Skip to main content

MHC/HLA Class I Loss in Cancer Cells

  • Chapter
  • First Online:
MHC Class-I Loss and Cancer Immune Escape

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1151))

Abstract

In this chapter I describe Tumour Immune Escape mechanisms associated with MHC/HLA class I loss in human and experimental tumours. Different altered HLA class-I phenotypes can be observed that are produced by different molecular mechanisms. Experimental and histological evidences are summarized indicating that at the early stages of tumour development there is an enormous variety of tumour clones with different MHC class I expression patterns. This phase is followed by a strong T cell mediated immune-selection of MHC/HLA class-I negative tumour cells in the primary tumour lesion. This transition period results in a formation of a tumour composed only of HLA-class I negative cells. An updated description of this process observed in a large variety of human tumors is included. In the second section I focus on MHC/HLA class I alterations observed in mouse and human metastases, and describe the generation of different tumor cell clones with altered MHC class I phenotypes, which could be similar or different from the original tumor clone. The biological and immunological relevance of these observations is discussed. Finally, the interesting phenomenon of metastatic dormancy is analyzed in association with a particular MHC class I negative tumor phenotype.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abril E, Mendez R, Garcia A, Serrano A, Cabrera T, Garrido, Ruiz-Cabello (1996) Characterization of a gastric tumor cell line defective in MHC class I inducibility by both alpha and gamma interferon. Tissue Antigens 47:391–398

    Article  CAS  PubMed  Google Scholar 

  • Abril E, Real LM, Serrano A, Jimenez P, Garcia A, Canton J, Trigo I, Garrido F, Ruiz-Cabello F (1998) Unresponsiveness to interferon associated with STAT1 protein deficiency in a gastric adenocarcinoma cell line. Cancer Immunol Immunother 47:113–120

    Article  CAS  PubMed  Google Scholar 

  • Aguirre-Ghiso JA (2002) Inhibition of FAK signaling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo. Oncogene 21:2513–2524

    Article  PubMed  Google Scholar 

  • Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7:834–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Algarra I, Ohlen C, Perez M, Ljunggren HG, Klein G, Garrido F, Karre K (1989) NK sensitive and lung clearance of MHC class-I deficient cells within a heterogeneous fibrosarcoma. Int J Cancer 44:675–680

    Article  CAS  PubMed  Google Scholar 

  • Algarra I, Gaforio JJ, Garrido A, Mialdea MJ, Perez M, Garrido F (1991) Heterogeneity of MHC-class-I antigens in clones of methylcholanthrene-induced tumors. Implications for local growth and metastasis. Int J Cancer Suppl 6:73–81

    Article  CAS  PubMed  Google Scholar 

  • Algarra I, Collado A, Garrido F (1997) Altered MHC class I antigens in tumours. Int J Clin Lab Res 27:95–102

    Article  CAS  PubMed  Google Scholar 

  • Algarra I, Gaforio JJ, Cabrera T, Collado A, Garrido F (1999) The biological consequences of altered MHC class I expression in tumours. J Biol Regul Homeost Agents 13:90–96

    CAS  PubMed  Google Scholar 

  • Algarra I, Cabrera T, Garrido F (2000) The HLA crossroad in tumor immunology. Hum Immunol 61:65–73

    Article  CAS  PubMed  Google Scholar 

  • Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and non classical MHC class I molecules: implications for tumour immune escape. Cancer Immunol Immunother 53:904–910

    Article  CAS  PubMed  Google Scholar 

  • Amiot L, Onno L, Lamy T, Dauriac C, Le Prise PY, Fauchet R, Drenou B (1998) Loss of HLA molecules in B lymphomas is associatedwith and aggressive clinical course. Br J Haematol 100:655–663

    Article  CAS  PubMed  Google Scholar 

  • Angell TE, Lechner MG, Jang JK, LoPresti JS, Epstein AL (2014) MHC class I loss is a frequent mechanism of immune escape in papillary thyroid cancer that is reversed by interferon and selumetinib treatment in vitro. Clin Cancer Res 20:6034–6044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aptsiauri N et al (2007) MHC class I antigens and immune surveillance in transformed cells. Int Rev Cytol 256:139–189

    Article  CAS  PubMed  Google Scholar 

  • Aptsiauri N, Cabrera T, Garcia-Lora A, Ruiz-Cabello F, Garrido F (2008) HLA class I expression, tumour escape and cancer progression. Curr Cancer Ther Rev 5:105–110

    Article  Google Scholar 

  • Aptsiauri et al (2014) ‘Hard’ and ‘soft’ loss of MHC class I expression in cancer cells. In: Rees R (ed) Tumor immunology and immunotherapy. Oxford University Press, Oxford, pp 63–78

    Google Scholar 

  • Aptsiauri N, Ruiz-Cabello F, Garrido F (2018) The transition from HLA-I positive to HLA-I negative primary tumors:the road to escape from T cell responses. Curr Opin Immunol 51:1–10

    Article  CAS  Google Scholar 

  • Aruga A, Aruga E, Tanigawa K, Bishop DK, Sondak VK, Chang AE (1997) Type I versus type 2 cytokine release by V beta T cell subpopulations determines in vivo anti-tumor reactivity IL-10 mediates a suppressive role. J Immunol 159(2):664–673

    CAS  PubMed  Google Scholar 

  • Bander N, Yao D, Liu H, Chen Y, Steiner M, Zuccaro W, Moy P (1997) MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and gamma. Prostate 33:233–239

    Article  CAS  PubMed  Google Scholar 

  • Bandoh N, Ogino T, Katayama A, Takahara M, Katada A, Hayashi A, Harabuchi Y (2010) HLA class I antigens and transporter associated with antigen processing downregulation in metastatic lesions of head and neck squamous cell carcinoma as a marker of poor prognosis. Oncol Rep 23(4):933–939

    Article  CAS  PubMed  Google Scholar 

  • Bartholomew JS, Glenville S, Sarkar S, Burt DJ, Stanley MA, Ruiz-Cabello F, Chengang J, Garrido F, Stern P (1997) Integration of high-risk human papillomavirus DNA is linked to the downregulation of class I human leucocyte antigens by steroid hormones in cervical tumor cells. Cancer Res 57:937–942

    CAS  PubMed  Google Scholar 

  • Benitez R, Godelaine D, Lopez-Nevot MA, Brasseur F, Jimenez P, Marchand M, Oliva MR, van Baren N, Cabrera T, Andry G, Landry C, Ruiz-Cabello F, Boon T, Garrido F (1998) Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides. Tissue Antigens 52:520–529

    Article  CAS  PubMed  Google Scholar 

  • Berah M, Hors J, Dausset J (1970) A study of HLA antigens in human organs. Transplantation 9:185

    Article  CAS  PubMed  Google Scholar 

  • Bernal M, Ruiz-Cabello F, Concha A, Paschen A, Garrido F (2012a) Implication of the β2-microglobuline gene in the generation of tumour escape phenotypes. Cancer Immunol Immunother 61(9):1359–1371

    Article  PubMed  CAS  Google Scholar 

  • Bernal M, Garcia F, Concha A, Blanco A, Garrido F, Ruiz-Cabello (2012b) Genome-wide differential genetic profiling characterize CRCs with genetic instability and specific routes to HLA class I loss and immunoescape. Cancer Immunol Immunother. June 61(6):803–816

    CAS  Google Scholar 

  • Bernards R, Schrier PI, Houwelling A, Bos JL, van der Eb EJ, Zijlstra M, Melief CJ (1983) Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. Nature 305:716–779

    Article  Google Scholar 

  • Bernards R, Desssain SK, Weinberg RA (1986) N-myc amplification causes down-regulation of MHC class I antigen expression in neuroblastoma. Cell 47:667–674

    Article  CAS  PubMed  Google Scholar 

  • Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C (2003) Long-term results and risk profiles of patients in five consecutive trials (1979–1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett 197:11–17

    Article  CAS  PubMed  Google Scholar 

  • Bicknell DC, Rowan A, Bodmer WF (1994) β2 microglobuline mutations: a study of stablished colorectal cell lines and fresh tumors. Proc Natl Acad Sci 91:4751–4755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bicknell DC, Kaklamanis L, Hampson R, Bodmer W, Karran P (1996) Selection for β2 microglobuline mutation in mismatch repair-defective colorectal carcinomas. Curr Biol 6(12):1695–1697

    Article  CAS  PubMed  Google Scholar 

  • Bijen C, Bantema-Joppe EJ, Jong R, Leffers N, Mourits M, Eggink H, van der Zee A, Hollema H, Bock G, Nijman H (2010) The prognostic role of classsical and nonclassical MHC class I expression in endometrial cancer. Int J Cancer 126:1417–1427

    CAS  PubMed  Google Scholar 

  • Blades RA, Keating P, McWillian LJ, George NJ, Stern P (1995) Loss of HLA class I expression in prostate cancer: implications for immunotherapy. Urology 46:681–686

    Article  CAS  PubMed  Google Scholar 

  • Blaschitz A, Lenfant F, Mallet V, Hartmann M, Bensussan A, Geraghty DE, Le Boutellier P, Dohr G (1997) Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur J Immunol 27:3380–3388

    Article  CAS  PubMed  Google Scholar 

  • Blom DJR, Luyten GPM, Mooy C, Kerkvliet S, Zwinderman AH, Jager MJ (1997) Human leucocyte antigen class I expression: marker of poor prognosis in uveal melanoma. Invest Ophtalmol Vis Sci 38:1865–1872

    CAS  Google Scholar 

  • Boesen M, Svane IM, Engel AM, Rygaard J, Thomsen AR, Werdelin O (2000) CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholantrene. Clin Exp Immunol 121:210–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonal J, Pareja E, Martin J, Romero C, Garrido F (1986) Repression of class I H-2K, H-2D antigens on GR9 methylcholantrene-induced tumour cell clones is related to the level of DNA methylation. J Immunogenet 13:179–186

    Article  CAS  PubMed  Google Scholar 

  • Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A (1994) Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 12:337–365

    Article  CAS  PubMed  Google Scholar 

  • Brady CS, Bartholomew JS, Burt DJ, Duggan-Keen MF, Glenville S, Telford N, Little AM, Davidson JA, Jimenez P, Ruiz-Cabello F, Garrido F, Stern PL (2000) Multiple mechanisms underlie HLA dysregulation in cervical cancer. Tissue Antigens 55:401–411

    Article  CAS  PubMed  Google Scholar 

  • Braud V, Allan D, Wilson D, McMichael A (1997) TAP and Tapasin dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol 8:1–10

    Article  Google Scholar 

  • Braud VM, Allan DS, O’Callaghan CA, Söderström K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A,B and C. Nature 391(6669):795–799

    Article  CAS  PubMed  Google Scholar 

  • Breslow A (1975) Tumor thickness, level of invasion and node dissection in stage 1 cutaneous melanoma. Ann Surg 182:572–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brouwer RE, van der Heiden P, Schreuder GM, Mulder A, Datema G, Anholts JD, Willemze R, Class FH, Falkenburg JH (2002) Loss or down regulation of HLA class I expression at the alleleic level in acute leukemia is infrequent but functionally relevant and can be restored by interferon. Hum Immunol 63(3):200–210

    Article  CAS  PubMed  Google Scholar 

  • Browning MJ, Krausa P, Rowan A, Bicnell DC, Bodmer JG, Bodmer WF (1993a) Tissue typing the HLA-locus from genomic DNA by sequence specific PCR: comparison of HLA phenotype and surface expression on colorectal tumor cells. Proc Natl Acad Sci USA 90:2842–2845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Browning MJ, Krausa P, Rowan A, Hill AB, Bicknell DC, Bodmer JG, Bodmer WF (1993b) Loss of human leukocyte antigen expression on colorectal tumors cell lines: implications for anti-tumor immunity and immunotherapy. J Immunother 14(3):163–168

    Article  CAS  Google Scholar 

  • Browning M, Petronzelli F, Bicknell D, Krausa P, Rowan A, Tonks S, Murray N, Bodmer J, Bodmer W (1996) Mechanisms of loss of HLA class I expression on colorectal tumor cells. Tissue Antigens 47(5):364–371

    Article  CAS  PubMed  Google Scholar 

  • Buckowitz A, Knaebel HP, Benner A, Blaker H, Gebert J, Kienle P, von Knebel DM, Kloor M (2005) Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastasis. Br J Cancer 92:1746–1753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burnet M (1957) Cancer: a biological approach. Br Med J 1:779–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27

    Article  CAS  PubMed  Google Scholar 

  • Buszello H, Ackermann R (1994) Immunohistochemical studies on the expression of HLA class I antigens in renal cell carcinoma: Comparison of primary and metastatic tumour tissue. Eur Uro. 25:158–163

    Article  CAS  Google Scholar 

  • Cabrera T, Concha A, Ruiz-Cabello F, Garrido F (1991) Loss of HLA heavy chain and β2 microglobuline in HLA negative tumours. Scand J Immunol 34:147–152

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Garrido V, Concha A, Martin J, Esquivias J, Oliva MR, Ruiz-Cabello F, Serrano S, Garrido F (1992) HLA molecules in basal cell carcinoma of the skin. Immunobiology 185:440–452

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Fernandez M, Sierra A, Garrido A, Herruzo A, Escobedo A, Fabra A, Garrido F (1996) High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol 50(2):127–134

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Salinero MA, Fernandez P, Jimenez P, Canton J, Garrido F (1997) HLA class I alterations in laryngeal tumors. In: Charron D (ed) HLA, genetic diversity of HLA. functional and medical implications, vol I, pp 543–545

    Google Scholar 

  • Cabrera T, Collado A, Fernandez MA, Ferron A, Sancho J, Ruiz-Cabello F, Garrido F (1998) High frequency of altered HLA class I phenotypes in invasive colorectal carcinomas. Tissue Antigens 52(2):114–123

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Salinero J, Fernandez MA, Garrido A, Esquivias J, Garrido F (2000) High frequency of altered HLA class I phenotypes in laryngeal carcinomas. Hum Immunol 61:499–506

    Article  CAS  PubMed  Google Scholar 

  • Cabrera CM, Jiménez P, Cabrera T, Esparza C, Ruiz-Cabello F, Garrido F (2003a) Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways: beta2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors. Tissue Antigens 61(3):211–219

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garrido F (2003b) Analysis of HLA expression in human tumor tissues. Cancer Immunol Immunother 52(1):1–9

    CAS  PubMed  Google Scholar 

  • Cabrera T, Pedrajas G, Cozar JM, Garrido A, Vicente J, Tallada M, Garrido F (2003c) HLA class I expression in bladder carcinomas. Tissue Antigens 62:324–327

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Maleno I, Lopez-Nevot MA, Redondo M, Fernandez MA, Collado A, Garrido F (2003d) High frequency of HLA-B44 allelic losses in human solid tumors. Hum Immunol 64:941–950

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Lara E, Romero JM, Maleno I, Real LM, Ruiz-Cabello F, Valero P, Camacho FM, Garrido F (2007) HLA class I expression in metastatic melanoma correlates with tumour development during autologous vaccination. Cancer Immunol Immunother 56(5):709–717

    Article  CAS  PubMed  Google Scholar 

  • Cai MY, Xu YF, Qiu SJ, Ju MJ, Gao Q, Li YW, Zhang BH, Zhou J, Fan J (2009) Human leucocyte antigen-G protein expression is an unfavourable prognostic factor predictor of hepatocellular carcinoma following curative resection. Clin Cancer Res 15:4686–4693

    Article  CAS  PubMed  Google Scholar 

  • Campoli M, Ferrone S (2008) HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 27(45):5869–5885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campoli M, Chang CC, Ferrone S (2002) HLA class I antigen loss, tumor immune escape and immune selection. Vaccine 20:A40–A45

    Article  CAS  PubMed  Google Scholar 

  • Carbone DP (1997) The biology of lung cancer. Semin Oncol 24(4):388–401

    CAS  PubMed  Google Scholar 

  • Carretero R, Romero JM, Ruiz-Cabello F, Maleno I, Rodriguez F, Camacho FM, Real LM, Garrido F, Cabrera T (2008) Analysis of HLA class I expression in progressing and regressing metastatic melanoma lesions after immunotherapy. Immunogenetics 60:439–447

    Article  CAS  PubMed  Google Scholar 

  • Carretero R, Cabrera T, Sáenz-López P, Maleno I, Aptsiauri N, Cózar JM, Garrido F (2011) Bacillus Calmette-Guerin immunotherapy of bladder cancer induces selection of human leukocyte antigen class I-deficient tumor cells. Int J Cancer 129(4):839–846

    Article  CAS  PubMed  Google Scholar 

  • Carretero FJ, Del Campo AB, Flores-Martin JF, Mendez R, Garcia-Lopez C, Cozar JM, Adams V, Ward S, Cabrera T, Ruiz-Cabello F, Garrido F, Aptsiauri N (2016) Frequent HLA class I alterations in human prostate cancer: molecular mechanisms and clinical relevance. Cancer Immunol Immunother 65:47–59

    Article  CAS  PubMed  Google Scholar 

  • Carretero FJ, Del Campo AB, Zinchenko S, Garrido F, Aptsiauri N (2017) Recovery HLA-A2 and beta2-microglobulin expression in tumor cells using viral vectors. J Cancer Sci Therapy 9:622–629

    CAS  Google Scholar 

  • Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nuñez G, Dalton WS, Jove R (1999) Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10(1):105–115

    Article  CAS  PubMed  Google Scholar 

  • Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla Favera R (2011) Combine genetic inactivation of β2 microglobuline and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20:728–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang CC, Ferrone S (2003) HLA G in melanoma: can the current controversies be solved? Semin Cancer Biol 13:361–369

    Article  CAS  PubMed  Google Scholar 

  • Chen HL, Gabrilovich D, Virmani A, Ratnani I, Girgis KR, Nadaf-Rahrov S, Fernandez-Viña M, Carbone DP (1996a) Structural and functional analysis of β2 microglobuline abnormalities in human lung and breast cancer. Int J Cancer 67(6):756–763

    Article  CAS  PubMed  Google Scholar 

  • Chen HL, Gabrilovich D, Tampe R, Girgis KR, Nadaf S, Carbone DP (1996b) A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nat Genet 13(2):210–213

    Article  CAS  PubMed  Google Scholar 

  • Cheng NC, Beitsma M, Chan A, Op den Camp I, Westerveld A, Pronk J, Versteeg R (1996) Lack of HLA class I expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus. Oncogene 13:1737–1744

    CAS  PubMed  Google Scholar 

  • Cherif I, Allory Y, Commo F, Gattegno B, Callard P, Paul P (2003) Altered pattern of major histocompatibility complex expression in renal cell carcinoma. Am J Pathol 162, n°2 501-508.

    Google Scholar 

  • Clark WH, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–726

    PubMed  Google Scholar 

  • Cochran AJ, Wen DR, Stene M, Fairhurst MV, Hoon DS (1988) Immunobiology of human cutaneous melanoma. Prog Clin Biol Res 256:597–618

    CAS  PubMed  Google Scholar 

  • Concha A, Cabrera T, Ruiz-Cabello F, Garrido F (1991a) Can the HLA phenotype be used as a prognostic factor in breast carcinomas? Int J Cancer Suppl 6:146–154

    Article  CAS  PubMed  Google Scholar 

  • Concha A, Esteban F, Cabrera T, Ruiz-Cabello F, Garrido F (1991b) Tumor aggressiveness and MHC class I and II antigens in laryngeal and breast cancer. Semin Cancer Biol 2:47–54

    CAS  PubMed  Google Scholar 

  • Connor ME, Stern PL (1990) Loss of MHC class-I expression in cervical carcinomas. Int J Cancer 46(6):1029–1034

    Article  CAS  PubMed  Google Scholar 

  • Cordon-Cardo C, Fuks Z, Drobnjak M, Moreno C, Eisenbach L, Feldman M (1991) Expression of HLA-A,B,C antigens on primary and metastatic tumor cell populations of human carcinomas. Cancer Res 51:6372–6380

    CAS  PubMed  Google Scholar 

  • Corrias MV, Scaruffi P, Occhino M, De Bernardi B, Tonini GP, Pistoia V (1996) Expression of MAGE-1, MAGE-3 and MART-1 genes in neuroblastoma. Int J Cancer 69:403–407

    Article  CAS  PubMed  Google Scholar 

  • Corrias MV, Ochino M, Croce M, De Ambrosis A, Pistillo MP, Bocca P, Pistoia V, Ferrini S (2001) Lack of HLA class I antigens in human neuroblastoma cells: analysis of its relationship to TAP and tapasin expression. Tissue Antigens 57:110–117

    Article  CAS  PubMed  Google Scholar 

  • Cozar JM, Apsiauri N, Tallada M, Garrido F, Ruiz-Cabello F (2008) Late pulmonary metastases of renal cell carcinoma immediately after post-transplantation immunosuppressive treatment: a case report. J Med Case Rep 2:111

    Article  PubMed  PubMed Central  Google Scholar 

  • Cromme FV, Airey J, Heemels MT, Ploegh HL, Keating PJ, Stern PL, Meijer CJ, Walboomers JM (1994) Loss of transporter protein encoded by the TAP-1 gene is highly correlated with loss of HLA expression in cervical carcinomas. J Exp Med 179:335–340

    Article  CAS  PubMed  Google Scholar 

  • Csiba AS, Whitwell HL, Moore M (1984) Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasia. Br J Cancer 50:699–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curiliano G, Criscitiello C, Gelao L, Goldhirsch A (2013) Molecular pathways: human leucocyte antigen G (HLA-G). Clin Cancer Res 19:5564–5571

    Article  CAS  Google Scholar 

  • D’Alessandro G, Zardawi I, Grace J, McCarthy W, Hersey P (1987) Immunohistological examination of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma. Pathology 19(4):339–346

    Article  PubMed  Google Scholar 

  • D’Urso CM, Wang CG, Cao Y, Tatake R, Zeff RA, Ferrone S (1991) Lack of HLA class I antigen expression by cultured FO-1 melanoma cells due to a defect in β2 microglobuline expression. J Clin Invest 87:284–292

    Article  PubMed  PubMed Central  Google Scholar 

  • Daar AS, Fuggle SV, Fabre JV, Ting A, Morris PJ (1984) The detailed distribution of HLA-A,B C antigens in normal human organs. Transplantation 38:287–292

    Article  CAS  PubMed  Google Scholar 

  • Davies B, Hiby L, Gardner L, Loke YW, King A (2001) HLA-G expression by tumours. Am J Reprod Immunol 45:103–107

    Article  CAS  PubMed  Google Scholar 

  • De Jong RA, Boerma A, Boezen HM, Mourits MJ, Hollema H, Nijman HW (2012) Loss of HLA class I and mismacht repair protein expression in sporadic endometroid endometrial carcinomas. Int J Cancer 131(8):1828–1836

    Article  PubMed  CAS  Google Scholar 

  • De Kruijf E, Sajet A, van Nes J, Natanov R, Putter H, Smit V, Liefers G, van den Elsen P, van de Velde C, Kuppen P (2010) HLA-E and HLA-G expression in classical HLA class I-negative tumors is a prognostic value for clinical outcome of early breast cancer patients. J Immunol 185:7452–7459

    Article  PubMed  CAS  Google Scholar 

  • De Nooij-van Dalen AG, van Buuren-van Seggelen VH, Lohman PH, Giphart M (1998) Chromosome loss with comcomitant duplication and recombination both contribute most to loss of heterozygosity in vitro. Genes Chromosome Cancer 21:30–38

    Article  Google Scholar 

  • De Waard-Siebinga I, Houbiers JGA, Hilders CGJ, de Wolff-Rouendaal D, Jager MJ (1996) Differential expression of HLA-A and B alleles on uveal melanoma as determined by immunohistology. Ocul Immnol Inflamm 4:1–14

    Article  Google Scholar 

  • del Campo AB, Kyte JA, Carretero J, Zinchencko S, Mendez R, Gonzalez-Aseguinolaza G, Ruiz-Cabello F, Aamdal S, Gaudernack G, Garrido F, Aptsiauri N (2014) Immune escape of cancer cells with β2 microglobuline loss over the course of metastatic melanoma. Int J Cancer 134(1):102–113

    Article  CAS  PubMed  Google Scholar 

  • Demanet C, Mulder A, Deneys V, Worsham MJ, Maes P, Claas FH, Ferrone S (2004) Down-regulation of HLA-A and HLA-Bw6 but not HLA-Bw4 allospecificities in leukemic cells: an escape mechanism from CTLs and NK attack. Blood 103(8):3122–3130

    Article  CAS  PubMed  Google Scholar 

  • Dengjel J, Nastke MD, Gouttefangeas C, Gitsioudis G, Schoor O, Altenberend F, Muller M, Krämer B, Missiou A, Sauter M, Hennenlotter J, Wernet D, Stenzl A, Rammensee HG, Klingel K, Stevanovic S (2006) Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas. Clin Cancer Res 12:4163–4170

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanisms of immune evasion. Nat Med 8(8):793–800

    Article  CAS  PubMed  Google Scholar 

  • Dovhey SE, Ghosh NS, Wright KL (2000) Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line. Cancer Res 60(20):5789–5796

    CAS  PubMed  Google Scholar 

  • Drenou B, Tilanus M, Semana G, Alizadeh M, Birebent B, Grosset JM, Dias P, van Wichen D, Arts Y, De Santis D, Fauchet R, Amniot L (2004) Loss of heterozygosity, a frequent but a non-exclusive mechanism responsible for HLA dysregulation in non-Hodgkin’s lymphomas. Br J Haematol 127:40–49

    Article  CAS  PubMed  Google Scholar 

  • Dunn GP, Sheehan KCF, Old LJ, Schreiber RD (2005) IFN unresponsiveness in LNCaP cells due to the lack of JAK1 gene expression. Cancer Res 65(8):3447–3453

    Article  CAS  PubMed  Google Scholar 

  • Durrant LG, Ballantyne KC, Armitage NC, Robins RA, Marksman R, Hardcastle JD, Baldwin RW (1987) Quantitation of MHC antigen expression on colorectal tumours and its association with tumour progression. Br J Cancer 56:425–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisen A, Weber B (1998) Recent advances in breast cancer biology. Curr Opin Oncol 10:486–491

    Article  CAS  PubMed  Google Scholar 

  • Eisenbach L, Segal S, Feldman M (1983) MHC imbalance and metastatic spread in Lewis lung carcinoma clones. Int J Cancer 32:113

    Article  CAS  PubMed  Google Scholar 

  • Ericsson C, Seregard S, Bartolazzi A, Levitskaya E, Ferrone S, Kiessling R, Larsson O (2001) Association of HLA class I and class II antigen expression and mortality in uveal melanoma. Invest Ophthalmol Visual Sci Vol 42, n°10,2153-2156.

    Google Scholar 

  • Erlich P (1909) The state of the art of cancer reseach. Ned Tijdschr Geneeskd 5:273–290

    Google Scholar 

  • Ernstoff MS, Duray P, Stenn K, Kirwood J (1985) Antigenic phenotype of pigment cell lesions: a study of melanoma, its precursor lesions and heterogeneity in metastatic melanoma. J Invest Dermatol 84:430–432

    Article  CAS  PubMed  Google Scholar 

  • Esteban F, Concha A, Huelin C, Perez-Ayala M, Pedrinaci S, Ruiz-Cabello F, Garrido F (1989) Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx. Int J Cancer 43:436–442

    Article  CAS  PubMed  Google Scholar 

  • Esteban F, Concha A, Delgado M, Perez-Ayala M, Ruiz-Cabello F, Garrido F (1990) Lack of MHC class I antigens and tumour agresiveness of the squamous cell carcinoma of the larynx. Br J Cancer 62:1047–1051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Esteban F, Redondo M, Delgado M, Garrido F, Ruiz-Cabello F (1996) MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up. Br J Cancer 74:1801–1804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eyal A, Levin I, Segal S, Levi I, Klein B, Kuperman O (1990) Variation of HLA-ABC surface antigen expression on adenocarcinoma of the colon in correlation with the degree of differentiation. Nat Immun Cell Growth Regul 9:222–227

    CAS  PubMed  Google Scholar 

  • Facoetti A, Nano N, Zelini P, Morbini P, Benericetti E, Ceroni M, Campoli M, Ferrone S (2005) Human leucocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res 11(23):8304–8311

    Article  CAS  PubMed  Google Scholar 

  • Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767

    Article  CAS  PubMed  Google Scholar 

  • Feenstra M, Rozemuller E, Duran K, Stuy I, van del Tweel J, Slootweg P, de Weger R, Tilanus M (1999a) Mutation in the β2m gene is not a frequent event in head and neck squamous cell carcinomas. Hum Immunol 60(8):697–706

    Article  CAS  PubMed  Google Scholar 

  • Feenstra M, Veltkamp M, Van Kuik J, Wierstma S, Slootweg P, van Den Tweel J, De Weger R, Tilanus M (1999b) HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas. Tissue Antigens 54:235–245

    Article  CAS  PubMed  Google Scholar 

  • Feenstra M, Verdaasdonk M, van der Zwan AW, de Weger R, Slootweg P, Tilanus M (2000) Microsatellite analysis of microdisected tumor cells and 6p high density analysis in head and neck squamous cell carcinomas with down-regulated human leukocyte antigen class I expression. Lab Invest 80(3):405–414

    Article  CAS  PubMed  Google Scholar 

  • Fernandez JE, Concha A, Aranega A, Ruiz-Cabello F, Cabrera T, Garrido F (1991) HLA class I and II expression in rhabdomyosarcomas. Immunobiology 182:440–448

    Article  CAS  PubMed  Google Scholar 

  • Fernandez MA, Ruiz-Cabello F, Oliva MR, Cabrera T, Jimenez P, Lopez Nevot MA, Garrido F (2000) β2-microglobulin gene mutation is not a common mechanism of HLA class I total loss in human tumors. Int J Clin Lab Res 30:87–92

    CAS  PubMed  Google Scholar 

  • Ferron A, Perez-Ayala M, Concha A, Cabrera T, Redondo M, Oliva MR, Ruiz-Cabello F, Garrido F (1989) MHC class I and II antigens on gastric carcinomas and autologous mucosa. J Immunogenet 16:413–423

    Article  CAS  PubMed  Google Scholar 

  • Fidler I (1970) Metastasis: Quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-Iodo-2-deoxyuridine. J Natl Cancer Inst 45(4):773–782

    CAS  PubMed  Google Scholar 

  • Fidler I (1973) Selection of successive tumor lines for metastasis. Nature New Biol 242:148–149

    Article  CAS  PubMed  Google Scholar 

  • Fidler I (1975) Biological behavior of malignant melanoma cells correlated to their survival in vivo. Cancer Res 35(1):218–224

    CAS  PubMed  Google Scholar 

  • Fidler I, Kripke M (1977) Metastasis results from preexisting variant cells whitin a malignant tumor. Science 197:893–895

    Article  CAS  PubMed  Google Scholar 

  • Fleming K, McMichael A, Morton JA, Woods J, McGee JO (1981) Distribution of HLA class I antigens in normal human tissue and in mammary cancer. J Clin Pathol 34:779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frumento G, Franchello S, Palmisano GL, Nicotra MR, Giacomini P, Loke YW, Geragthy DE, Maio M, Manzo C, Natali PG, Ferrara GB (2000) Melanomas and melanoma cell lines do not express HLA-G and the expression cannot be induced by gamma IFN treatment. Tissue Antigens 56(1):30–37

    Article  CAS  PubMed  Google Scholar 

  • Fukushima Y, Oshika Y, Nakamura M, Tokunaga T, Hatanaka H, Abe Y, Yamazaki H, Kijima H, Ueyama Y, Tamaoki N (1998) Increase expression of human histocompatibility leukocyte antigen-G in colorectal cancer cells. Int J Mol Med 2:349–351

    CAS  PubMed  Google Scholar 

  • Galon J, Costes A, Sanchez Cabo F, Kirilovsky A, Mlenick B, Lagorde-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Brouneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Lora A, Algarra I, Gaforio JJ, Ruiz-Cabello F, Garrido F (2001) Immunoselection by T lymphocytes generates repeated MHC class I deficient metastatic tumor variants. Int J Cancer 91:109–119

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Lora A, Martinez M, Algarra I, Gaforio JJ, Garrido F (2003a) MHC class I-deficient metastatic tumor variants immunoselected by T lymphocytes originate from the coordinated downregulation of APM components. Int J Cancer 106:521–527

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Lora A, Algarra I, Collado A, Garrido F (2003b) Tumour immunology, vaccination and escape strategies. Eur J Immunogenet 30:177–183

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Lora A, Algarra I, Garrido F (2003c) MHC class I antigens, immune surveillance and tumor immune escape. J Cell Physiol 195:346–355

    Article  CAS  PubMed  Google Scholar 

  • Garrido F (1987) The biological implications of the abnormal expression of MHC antigens on murine and human tumours. In: David CS (ed) H-2 gene complex: genes, molecules, function, Nato ASI series, vol 144. Plenum Press, pp 623–639

    Google Scholar 

  • Garrido F, Algarra I (2001) MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 83:117–158

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Klein E (1991a) MHC antigen expression I. In: Klein E, Garrido (eds) Experimental tumours. Seminars in cancer biology, vol 2-1. Saunders Scientific Publications, pp 1–2

    Google Scholar 

  • Garrido F, Klein E (1991b) MHC antigen expression II. In: Klein E, Garrido (eds) Experimental tumours. Seminars in cancer biology, vol 1. Saunders Scientific Publications, pp 1–2

    Google Scholar 

  • Garrido F, Ruiz-Cabello F (1991) MHC expression on human tumors. Its relevance for local tumour growth and metastasis. Semin Cancer Biol 2:3–10

    CAS  PubMed  Google Scholar 

  • Garrido F, Schirrmacher V, Festenstein H (1977) Studies on H-2 specificities on mouse tumour cells by a new microradioassay. J Immunogenet 4:15–27

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Perez M, Torres MD (1979) Absence of four H-2d antigenic specificites in an H-2d sarcoma. J Immunogenet 6(2):83–86

    Article  CAS  PubMed  Google Scholar 

  • Garrido A, Perez M, Delgado C, Garrido ML, Rojano J, Algarra I, Garrido F (1986a) Influence of class I H-2 gene expression on local tumor growth. Description of a model obtained from clones derived from a solid BALB/c tumor. Exp Clin Immunogenet 3(2):98–110

    CAS  PubMed  Google Scholar 

  • Garrido ML, Perez M, Delgado C, Rojano J, Algarra I, Garrido A, Garrido F (1986b) Immunogenicity of H-2 positive and H-2 negative clones of a mouse tumour, GR9. J Immunogenet 13(2–3):159–167

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Cabrera T, Concha A, Glew S, Ruiz-Cabello F, Stern PL (1993) Natural history of HLA expression during tumour development. Immunol Today 14:491–499

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Cabrera T, Lopez-Nevot MA, Ruiz-Cabello F (1995) HLA class I antigens in human tumors. Adv Cancer Res 67:155–195

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, LopezBotet M, Duggan-Keen M, Stern PL (1997a) Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today 18:89–95

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Cabrera T, Accolla RS, Bensa JC, Bodmer W, Dohr G, Drouet M, Fauchet R, Ferrara GB, Ferrone S, Giacomini P, Kageshita T, Koopman L, Maio M, Marincola F, Mazzilli C, Morel PA, Murray A, Papasteriades CRH, Salvaneschi L, Stern PL, Ziegler A (1997b) HLA and cancer: 12th international histocompatibility workshop study. HLA, Genetic diversity of HLA. Functional and medical implications. vol. I. In: Charron D, EDK (eds), pp 445–452

    Google Scholar 

  • Garrido F, Cabrera T, Aptsiauri N (2010a) “Hard” and “Soft” lesions underlying the HLA class I alterations in cancer cells: implications for immunotherapy. Int J Cancer 127(2):249–256

    CAS  PubMed  Google Scholar 

  • Garrido F, Algarra I, García-Lora AM (2010b) The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions. Cancer Immunol Immunother 59(10):1601–1606

    Article  CAS  PubMed  Google Scholar 

  • Garrido C, Paco L, Romero I, Berruguilla E, Stefansky J, Collado A, Algarra I, Garrido F, Lora G (2012) MHC class I molecules act as tumour suppressor genes regulating the cell cycle gene expression, invasion and intrinsic tumorigenicity of melanoma cells. Carcinogenesis 33(3):687–693

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Aptsiauri N, Doorduijn E, Garcia-Lora A, van Hall T (2016a) The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr Opin Immunol 39:44–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido F, Romero I, Aptsiauri N, Garcia-Lora AM (2016b) Generation of MHC class I diversity in primary tumors and selection of the malignant phenotype. Int J Cancer 138:271–280

    Article  CAS  PubMed  Google Scholar 

  • Garrido F, Perea F, Bernal M, Sanchez-Palencia A, Aptsiauri N, Ruiz-Cabello F (2017) The escape of cancer from T cell-mediated immune surveillance: HLA class I loss and tumor tissue architecture. Vaccines 5:7. https://doi.org/10.3390/vaccines5010007

    Article  CAS  PubMed Central  Google Scholar 

  • Garrido MA, Rodriguez T, Zinchenko S, Maleno I, Ruiz-Cabello F, Concha A, Olea N, Garrido F, Aptsiauri N (2018) HLA-I alterations in breast carcinoma are associated with a high frequency of the loss of heterozygosity at chromosome 6 and 15. Immunogenetics. https://doi.org/10.1007/s00251-018-1074-2

    Article  CAS  PubMed  Google Scholar 

  • Geragthy D (1993) Structure of the HLA class I region and expression of its resident genes. Curr Opin Immunol 5:3–7

    Article  Google Scholar 

  • Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, Bahl S, Cao Y, Amin-Mansour A, Yamauchi M, Sukawa Y, Stewart C, Rosenberg M, Mima K et al (2016) Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep 15:857–865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111(1):58–64

    Article  CAS  PubMed  Google Scholar 

  • Goeppert B, Frauenschuh L, Zucknick M, Stenzinger A, Andrulis M, Klauschen F, Joehrens K, Warth A, Renner M, Mehrabi A, Hafezi M, Thelen A, Schirrmacher P, Weichert W (2013) Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer. Br J cancer 109(10):2665–2674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goeppert B, Frauenschuh L, Zucknick M, Roessler S, Mehrabi A, Hafezi M, Stenzinger A, Warth A, Pathil A, Renner M, Schirrmacher P, Weichert W (2015) Major histocompatibility c0mplex class I expression impacts on patient survival and the composition of inflammatory infiltrate in biliary tract cancer. Br J Cancer 113(9):1343–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grandis JR, Falkner DM, Melhem MF, Gooding WE, Drenning SD, Morel PA (2000) Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clin Cancer Res 6(7):2794–2802

    CAS  PubMed  Google Scholar 

  • Grasso C, Giannakis M, Wells D, Hamada T, Mu X et al (2018) Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-17-1327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gutierrez J, Lopez-Nevot MA, Cabrera T, Oliva R, Esquivias J, Ruiz-Cabello, Garrido F (1987) Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness. Exp Clin Immunogenet 4:144–152

    CAS  PubMed  Google Scholar 

  • Hammerling G, Klar D, Katzav S, Segal S, Feldman M, Wallich R, Hammerling A (1986) Manipulation of metastasis and tumor growth by transfection with histocompatibility class I genes. J Immunogenet 13:153–157

    Article  CAS  PubMed  Google Scholar 

  • Han LY, Fletcher DM, Urbauer DL, Mueller P, Landen CN, Kamat AA, Ling YG, Merrit WM, Spannuth WA, Deavers MT, De Geest K, Gershenson DM, Lutgendorf SK, Ferrone S, Sood AK (2008) HLA class I antigen processing machinery component expression and intratumoral T-cell infiltrate as independent prognostic markers in ovarian carcinoma. Clin Cancer Res 14(11):3372–3379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hicklin DJ, Wang Z, Arienti F, Rivoltini L, Parmiani G, Ferrone S (1998) β2-microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma. J Clin Invest 101:2720–2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hicklin DJ, Marincola F, Ferrone S (1999) HLA class I downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today 5:178–186

    Article  CAS  PubMed  Google Scholar 

  • Hilders CG, Houbiers JG, Krul EJ, Fleuren GJ (1994) The expression of histocompatibility-related leukocyte antigens in the pathway to cervical carcinoma. Am J Clin Pathol 101(1):5–12

    Article  CAS  PubMed  Google Scholar 

  • Hinz S, Trauzold A, Boenicke L, Sandberg C, Beckmann S, Bayer E, Walczak H, Kalthoff H, Ungefroren H (2000) Bcl-X-L protects pancreatic adenocarcinoma cells again CD95-and TRAIL- receptor mediated apoptosis. Oncogene 19(48):5477–5486

    Article  CAS  PubMed  Google Scholar 

  • Holzmann B, Bröker EB, Lehmann JM, Ruiter DJ, Sorg C, Riethmüller G, Johnson JP (1987) Tumour progression in human melanoma:five stages defined by their antigenic phenotypes. Int J Cancer 15 39(4):466–471

    Article  CAS  Google Scholar 

  • Hurks HM, Metzelaar-Blok JA, Mulder A, Claas FH, Jager MJ (2000) High frequency of allele-specific down-regulation of HLA class I expression in uveal melanoma cell lines. Int J Cancer 85:697–702

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim EC, Guerra N, Lacombe MJ, Angevin E, Chouaib S, Carosella ED, Caignard A, Paul P (2001) Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma. Cancer Res 61:6838–6845

    CAS  PubMed  Google Scholar 

  • Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208

    Article  CAS  PubMed  Google Scholar 

  • Imai D, Yoshizumi T, Okano S, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Soejima Y, Aishima S, Oda Y, Maehara Y (2017) The prognostic impact of programme cell death ligand 1 and human leucocyte antigen class I in pancreatic cancer. Cancer Med 6:1614–1626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colon carcinogenesis. Nature 363:558–561

    Article  CAS  PubMed  Google Scholar 

  • Ishigami S, Natsugoe S, Nakajo A, Arigami T, Kitazono M, Okumura H, Matsumoto M, Uchicado Y, Setoyama T, Sasaki K, Aikou T (2008) HLA-Class I expression in gastric cancer. Anticancer Res 97:605–608

    CAS  Google Scholar 

  • Jager E, Ringhoffer M, Karbach J, Arand M, Oesch F, Knuth A (1996) Inverse relation-ship of melanocyte differentiation antigen expression in melanoma tissues and CD8(+) cytotoxic T cell responses: evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer 66(4):470–476

    Article  CAS  PubMed  Google Scholar 

  • Jager E, Ringhoffer M, Altmannsberger M, Arand M, Karbach J, Jäger D, Oesch F, Knuth A (1997) Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer 71:142–147

    Article  CAS  PubMed  Google Scholar 

  • Jager MJ, Hurks HM, Levitskaya J, Kiessling R (2002) HLA expression in uveal melanoma: there is no rule without some exception. Hum Immunol 63:444–451

    Article  CAS  PubMed  Google Scholar 

  • Jimenez P, Canton J, Collado A, Cabrera T, Serrano A, Real LM, Garcia A, Ruiz-Cabello F, Garrido F (1999) Chromosome loss is the most frequent mechanism contributing to HLA haplotype loss in human tumors. Int J Cancer 83:91–97

    Article  CAS  PubMed  Google Scholar 

  • Jimenez P, Canton J, Concha A, Cabrera T, Fernandez M, Real LM, Garcia A, Serrano A, Garrido F, Ruiz-Cabello F (2000) Microsatellite instability analysis in tumors with different mechanisms for total loss of HLA expression. Cancer Immunol Immunother 48:684–690

    Article  CAS  PubMed  Google Scholar 

  • Jimenez P, Cabrera T, Mendez R, Esparza C, Cozar J, Tallada M, Lopez-Nevot MA, Ruiz-Cabello F, Garrido F (2001) A nucleotide insertion in exon 4 is responsible for the absence of expression of an HLA-A*0301 allele in a prostate carcinoma cell line. Immunogenetics 53:606–610

    Article  CAS  PubMed  Google Scholar 

  • Jordanova ES, Riemersma SA, Philippo K, Schuuring E, Kluin PM (2003) β2-microglobuline aberrations in diffuse large B cell lymphoma of the testis and the central nervous system. Int J Cancer 103:393–398

    Article  CAS  PubMed  Google Scholar 

  • Kaklamanis L, Hill A (1992) MHC loss in colorectal tumours: evidence for immunoselection? Cancer Surv 13:155–171

    CAS  PubMed  Google Scholar 

  • Kaklamanis L, Gatter KC, Hill AB, Mortensen N, Harris AL, Krausa P, McMichael A, Bodmer JG, Bodmer WF (1992) Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer. Int J Cancer 51:379–385

    Article  CAS  PubMed  Google Scholar 

  • Kaklamanis L, Townsend A, Doussis-Anagnostopoulou IA, Mortensen N, Harris AL, Gatter KC (1994) Loss of major histocompatibility complex-encoded transporter associated with antigen presentation (TAP) in colorectal cancer. Am J Pathol 145:505–509

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaklamanis L, Leek R, Koukourakis M, Gatter KC, Harris AL (1995) Loss of transporter in antigen processing-1 transport protein and major histocompatibility complex class I molecules in metastatic versus primary breast cancer. Cancer Res 55:5191–5194

    CAS  PubMed  Google Scholar 

  • Karamurzin Y, Rutgers JK (2009) DNA mismacht repair deficiency in endometrial carcinoma. Int J Gynecol Pathol 28(3):239–255

    Article  PubMed  Google Scholar 

  • Keating PJ, Cromme FV, Duggan-Keen M, Snijders PJ, Walboomers JM, Hunter RD, Dyer PA, Stern P (1995) Frequency of downregulation of individual HLA-A and B alleles in cervical carcinomas in relation to TAP-1 expression. Br J Cancer 72(2):402–411

    Article  Google Scholar 

  • Kersemaekers AM, Kenter GG, Hermans J, Fleuren GJ, van de Vijver MJ (1998) Allelic loss and prognosis in carcinoma of the uterine cervix. Int J Cancer 79:411–417

    Article  CAS  PubMed  Google Scholar 

  • Khazaie K, Prifti S, Beckhove P, Griesbach A, Russell S, Collins M, Schirrmacher V (1994) Persistence of dormant tumor cells in the bone marrow of tumor cell vaccinated mice correlates with long-term immunological protection. Proc Natl Acad Sci USA 91:7430–7434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of “tumour escape” phenotypes. Nat Immunol 3:999–1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kikuchi E, Yamazaki K, Torigoe T, Cho Y, Miyamoto M, Oizumi S, Hommura F, Dosaka-Akita H, Nishimura M (2007) HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer. Cancer Sci 98:1424–1430

    Article  CAS  PubMed  Google Scholar 

  • Kitamura H, Torigoe T, Honma I, Sato E, Asanuma H, Hirohashi Y, Sato N, Tsukamoto T (2006) Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instilation of Bacillus Calmette-Guerin immunotherapy for bladder cancer. Clin Cancer Res 12(15):4641–4644.52-461

    Article  Google Scholar 

  • Kitamura H, Honma I, Torigoe T, Asanuma H, Sato N, Tsukamoto T (2007) Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma. J Urol i77:1269–1272

    Article  CAS  Google Scholar 

  • Klein B, Klein T, Nyska A, Shapira J, Figer A, Schwartz A, Rakovsky E, Livni E, Lurie H (1991) Expression of HLA class I and class II in gastric carcinomas in relation to pathologic stage. Tumour Biol 12:68–74

    Article  CAS  PubMed  Google Scholar 

  • Klein B, Levin I, Klein T (1996) HLA class I antigens in human solid tumors. Isr J Med Sci 33:1238–1243

    Google Scholar 

  • Kloor M, von Knebel Doeberitz M (2016) The immune biology of microsatellite-unstable cancer. Trends Cancer 2(3):121–133

    Article  PubMed  Google Scholar 

  • Kloor M, Becker C, Benner A, Woerner SM, Gebert J, Ferrone S, von Knebel Doeberitz M (2005) Immunoselective preasure and human leucocyte antigen class I machinery defects in microsatellite unstable colorectal cancers. Cancer Res 65:6418–6424

    Article  CAS  PubMed  Google Scholar 

  • Kloor M, Michel S, Buckowitz B, Ruschoff J, Buttner R, Holinski-Feder E, Dippold W, Wagner R, Tariverdian M, Benner A, Schwitalle Y, Kuchenbuch B et al (2007) β2 microglobuline mutations in microsatellite unstable colorectal cancer. Int J Cancer 121:454–458

    Article  CAS  PubMed  Google Scholar 

  • Kloor M, Michel S, von Knebel Doeberitz M (2010) Immune evasion of microsatelite unstable colorectal cancers. Int J Cancer 127:1001–1010

    Article  CAS  PubMed  Google Scholar 

  • Koene GJ, Arts-Hilkes YH, van der Ven KJ, Rozemuller EH, Slootweg PJ, de Weger RA, Tilanus M (2004) High level of chromosome 15 aneuploidy in head and neck squamous cell carcinoma lesions identified by FISH analysis: Limited value of β2 microglobuline LOH analysis. Tissue Antigens 64:452–461

    Article  CAS  PubMed  Google Scholar 

  • Koopman LA, Mulder A, Corver WE, Anholts JD, Giphart MJ, Class FH, Fleuren GJ (1998) HLA class I phenotype and genotype alterations in cervical carcinomas and derivative cell lines. Tissue Antigens 51:623–636

    Article  CAS  PubMed  Google Scholar 

  • Koopman LA, Van der Slik AR, Giphart MJ, Fleuren (1999) Human leukocyte antigen class I gene mutations in cervical cancer. J Natl Cancer Inst 91:961–975

    Article  Google Scholar 

  • Koopman LA, Corver WE, van der Slik AR, Giphart MJ, Fleuren GJ (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191(6):961–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korkolopoulo P, Kaklamanis L, Pezella F, Harris AL, Gatter KC (1996) Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 73:148–153

    Article  Google Scholar 

  • Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R (1990) A class I antigen, HLA-G, expressed in human trophoblast. Science 248(4952):220

    Article  CAS  PubMed  Google Scholar 

  • Kripke M, Gruys E, Fidler I (1978) Metastatic heterogeneity of cells from an ultraviolet light-induced murine fibrosarcoma of recent origin. Cancer Res 38:2962–2967

    CAS  PubMed  Google Scholar 

  • Kruger T, Schoor O, Lemmel C, Kraemer B, Reichle C, Dengiel J, Weinschenk T, Muller M, Hennenlotter J, Stenzl A, Rammensee HG, Stevanovich S (2005) Lessons to be learned from primary renal cell carcinomas: novel tumor antigens and HLA ligands for immunotherapy. Cancer Immunol Immunother 54:826–836

    Article  PubMed  CAS  Google Scholar 

  • Kurokohchi K, Carrington M, Mann D, Simonis T, Alexander-Miller M, Feinstone SM, Akatsuka T, Berzofsky J (1996) Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma. Hepatology 23(5):1181–1188

    Article  CAS  PubMed  Google Scholar 

  • Lampson LA, Whelan JP, Fisher CA (1985) HLA-A,B,C and β2-microglobuline are expressed weakly by human cells of neuronal origin but can be induced in neuroblastoma cell lines by interferon. Prog Clin Biol Res 175:379–388

    CAS  PubMed  Google Scholar 

  • Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274

    Article  CAS  PubMed  Google Scholar 

  • Le Boutellier P (1997) HLA-G: on the track of immunological functions. Eur J Immunogenet 24:397–408

    Article  Google Scholar 

  • Le Boutellier P, Blaschitz A (1999) The functionality of HLA-G is emerging. Immunol Rev 167:233–244

    Article  Google Scholar 

  • Le YS, Kim TE, Kim BK et al (2002) Alterations of HLA class I and class II antigen expression in borderline invasive and metastatic ovarian cancers. Exp Mol Med 34:18–26

    Article  PubMed  Google Scholar 

  • Lee N, Llano M, Carretero A, Ishitani F, Navarro M, Lopez-Botet M, Geragthy D (1998) HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 95:5199–5204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H-W, Min SK, Y-S JU, Sung J, Lim MS, Yang DH, Lee BH (2011) Prognostic significance of HLA class I expressing in gastric carcinoma defined by monoclonal anti-Pan HLA class I antibody, EMR8-5. J Gastrointest Surg 15:1336–1343

    Article  PubMed  Google Scholar 

  • Lehmann F, Marchand M, Hainaut P, Puoillart P, Sastre X, Ikeda H, Boon T, Coulie PG (1995) Diferences in the antigens recognized by cytolytic T cells on two successive metastasis of a melanoma patient are consistent with immune selection. Eur J Immunol 25:340–347

    Article  CAS  PubMed  Google Scholar 

  • Levin MD, Klein T, Goldstein J, Kuperman O, Kanetti J, Klein (1991) Expression of class I histocompatibility antigens in transitional cell carcinoma of the urinary bladder in relation to survival. Cancer 68:2591–2594

    Article  CAS  PubMed  Google Scholar 

  • Levin I, Klein B, Segal S, Eyal A, Gopas J, Kanetti J, Saadon M, Kuperman O (1992) Expression of HLA class-I encoded cell surface antigens in transitional carcinoma of the urinary bladder. Tissue Antigens 39:19–22

    Article  CAS  PubMed  Google Scholar 

  • Levin I, Klein T, Kuperman O, Segal S, Shapira J, Gal R, Hart Y, Klein B (1994) The expression of HLA class I antigen in prostate in relation to tumor differentiation and patient survival. Cancer Detect Prev 18:443–445

    CAS  PubMed  Google Scholar 

  • Ling A, Zhang X, Zhou WJ, Ruan YY, Xu DP, Wang Q, Yan WH (2011) Human leukocyte antigen-G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma. Int J Cancer 129:1382–1390

    Article  CAS  Google Scholar 

  • Ljunggren HG, Karre K (1986) Experimental strategies and interpretations in the analysis of changes in MHC gene expression during tumor progression:opposing influences of T cell and natural killer cell mediated resistance. J Immunogenet 13:141–151

    Article  CAS  PubMed  Google Scholar 

  • Llano M, Lee N, Navarro F, Garcia P, Albar JP, Geraghty D, Lopez-Botet M (1998) HLA-E bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derive nonamer. Eur J Immunol 28:2854–2863

    Article  CAS  PubMed  Google Scholar 

  • Lohr J, Ratliff T, Huppertz A, Ge Y, Dictus C, Ahmadi R, Grau S, Hiraoka N, Eckstein V, Ecker RC, Korff T, von Deimling A, Unterberg A, Beckhove P, Herold-Mende C (2011) Effector T cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin Cancer Res 17:4296–4308

    Article  CAS  PubMed  Google Scholar 

  • Loke YW, King A (1991) Recent development in the human maternal-fetal immune interaction. Curr Opin Immunol 3:762–766

    Article  CAS  PubMed  Google Scholar 

  • Loke YW, Hiby S, King A (1999) Human leukocyte antigen G and reproduction. J Reprod Immunol 43:235–242

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Nevot MA, Garcia E, Pareja E, Bonal J, Martin J, Ruiz-Cabello F, Serrano S, Garrido F (1986) Differential expression of HLA class I and II antigens in primary and metastatic melanomas. J Immunogenet 13(2/3):219–227

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Nevot MA, Romero C, Ruiz-Cabello F, Pedrinaci S, Gutierrez J, Oliva MR, Huelin C, Garrido F (1987) Study of class I HLA genes in human tumours. In: Dupont B (ed) X international histocompatibility worshop, histocompatibility testing, New York, pp 473–474

    Google Scholar 

  • Lopez-Nevot MA, Garcia E, Romero C, Oliva MR, Serrano S, Garrido F (1988) Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. Exp Clin Immunogenet 5:203–212

    CAS  PubMed  Google Scholar 

  • Lopez-Nevot MA, Esteban F, Ferron A, Gutierrez J, Oliva MR, Romero C, Huelin C, Ruiz-Cabello F, Garrido F (1989) HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas. Br J Cancer 59:221–226

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Nevot MA, Ramal LM, Cabrera T, Ruiz-Cabello F, Garrido F (2002) HLA and cancer: β2-microglobuline mutations and malignant melanoma. In: Zierhut M, Jager M, Ksander B (eds) Immunology of ocular tumours. Swets and Zeitlinger, pp 91–101

    Google Scholar 

  • Lou Y, Vitalis TZ, Basha G, Cai B, Choi KB, JeVreis AP, Aliott WM, Atkins D, Seliger B, JeVries WA (2005) Restoration of the expression of transporters associated with antigen processing in lung carcinoma increases tumor-specific immune responses and survival. Cancer Res 65:7926–7933

    Article  CAS  PubMed  Google Scholar 

  • Lu QL, Abel P, Mitchell S, Foster C, Lalani EN (2000) Decrease HLA-A expression in prostate cancer is associated with normal allele dosage in the majority of cases. J Pathol. 190:169–176

    Article  CAS  PubMed  Google Scholar 

  • MacGranahan N, Rosenthal R, Hiley C, Rowan A, Watkins T, Wilson G, Birback N, Veeriah S, van Loo P, Herrero J, Swanton C, TRACERx Consortium (2017) Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171:1–13

    Article  CAS  Google Scholar 

  • Madjd Z, Spendlove I, Pinder S, Ellis I, Durrant L (2005) Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int J Cancer 117:248–255

    Article  CAS  PubMed  Google Scholar 

  • Main EK, Monos DS, Lampson LA (1988) IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allokilling and susceptible to non-MHC restricted cytotoxicity. J Immunol 141:2943–2950

    CAS  PubMed  Google Scholar 

  • Maiorana A, Cesinaro AM, Fano A, Collina G (1995) Expression of MHC class I and class II in primary breast carcinomas and synchrnous nodal metastases. Clin Exp Metastasis 13:43–48

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, Lopez-Nevot MA, Cabrera T, Salinero J, Garrido F (2002) Multiple mechanisms generate HLA class I altered phenotypes in laryngeal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozigocity in chromosome region 6p21. Cancer Immunol Immunother 51:389–396

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, Cabrera CM, Cabrera T, Paco L, Lopez-Nevot MA, Collado A, Ferron A, Garrido F (2004a) Distribution of HLA class I altered phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Immunogenetics 56:244–253

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, Lopez-Nevot MA, Seliger B, Garrido F (2004b) Low frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21 in clear renal cell carcinomas. Int J Cancer 109:636–638

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, Romero JM, Cabrera T, Paco L, Aptsiauri N, Cozar JM, Tallada M, Lopez-Nevot MA, Garrido F (2006) LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas. Immunogenetics 58:503–510

    Article  CAS  PubMed  Google Scholar 

  • Maleno I, Aptsiauri N, Cabrera T, Gallego A, Paschen A, Lopez-Nevot MA, Garrido F (2011) Frequent loss of heterozygosity in the β2-microglobulin region of chromosome 15 in primary human tumors. Immunogenetics 63:65–71

    Article  CAS  PubMed  Google Scholar 

  • Marin R, Ruiz-Cabello F, Pedrinaci S, Mendez R, Jimenez P, Geraghty D, Garrido F (2003) Analysis of HLA-E expression in human tumors. Immunogenetics 54:767–775

    CAS  PubMed  Google Scholar 

  • Marincola FM, Shamamian P, Alexander RB, Gnarra JR, Turetskaya RL, Nedospasov SA, Simonis TB, Taubenberger JK, Yanelli J, Mixon et al (1994) Loss of HLA haplotype and B locus down-regulation in melanoma cell lines. J Immunol 153:1225–1237

    CAS  PubMed  Google Scholar 

  • Marincola F, White DE, Wise AP, Rosenberg SA (1995) Combination therapy with interferon alpha-2a and interleukin-2 for the treatment of metastatic cancer. J Clin Oncol 13:1110–1112

    Article  CAS  PubMed  Google Scholar 

  • Marincola FM, Jaffe EM, Hichklin DJ, Ferrone S (2000) Escape of solid human tumors from T cell recognition: molecular mechanisms and functional significance. Adv Immunol 74:181–273

    Article  CAS  PubMed  Google Scholar 

  • Martayan A, Fraioli R, Giorda E, Setini A, Ciccarelli G, Delfino L, Ferrara GB, Giacomini P (1999) Biosynthesis of HLA-C heavy chains in melanoma cells with multiple defects in the expression of HLA-A,B,C molecules. Br J Cancer 80(5–6):639–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Massucci MG, Torsteindottir S, Colombani J, Brautbar C, Klein E, Klein G (1987) Downregulation of class I HLA antigens of the Epstein-barr-virus encoded latent membrane protein in Burkitt lymphoma lines. Proc Natl Acad Sci (Was) 84:4567–4571

    Article  Google Scholar 

  • Matsui M, Machida S, Itani-Yohda T, Akatsuka T (2002) Downregulation of the proteasome subunits, transporter and antigen presentation in hepatocellular carcinoma and their restoration by interferon-γ. J Gastroenterol Hepatol 17:897–907

    Article  CAS  PubMed  Google Scholar 

  • Mattijssen V, de Mulder PH, Schalkwijk L, Manni B, Van’t Hof-Grootenboer, Ruiter DJ (1991) HLA antigen expression in routinely processed head and neck squamous cell carcinoma primary lesions of different sites. Int J Cancer Suppl 6:95–100

    Article  CAS  PubMed  Google Scholar 

  • Mazurenko N, Attaleb M, Gritsko T, Semjonova L, Pavlova L, Sakharova O, Kisseljov F (1999) High resolution mapping of chromosome 6 deletion in cervical cancer. Oncol Rep 6(4):859–863

    CAS  PubMed  Google Scholar 

  • Mehta AM, Jordanova ES, Kenter GC, Ferrone S, Fleuren GJ (2008) Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother 57:197–206

    Article  CAS  PubMed  Google Scholar 

  • Meissner M, Reichert TF, Kunkel M, Gooding W, Whiteside TL, Ferrone S, Seliger B (2005) Defects in the human leucocyte antigen class I processing machinery in head and neck squamous cell carcinomas: association with clinical outcome. Clin Cancer Res 11(7):2552–2560

    Article  CAS  PubMed  Google Scholar 

  • Mendez R, Serrano A, Jager E, Maleno I, Ruiz-Cabello F, Knuth A, Garrido F (2001) Analysis of HLA class I expression in different metastases from two melanoma patients undergoing peptide immunotherapy. Tissue Antigens 57:508–519

    Article  CAS  PubMed  Google Scholar 

  • Mendez R, Ruiz-Cabello F, Jimenez P, Paschen A, Knuth A, Jager E, Traversari C, Shadendorf D, Boon T, Garrido F (2006) Impact of HLA class I alterations in patients undergoing T cell-specific immunotherapy. 13th IHWC. Immunobiology of the Human MHC. Proceedings of the 13th international histocompatibility workshop and conference. Vol II, IHWC Press, pp 512–514.

    Google Scholar 

  • Mendez R, Ruiz-Cabello F, Rodriguez T, Del Campo A, Paschen A, Schadendorf D, Garrido F (2007) Identification of different tumor escape mechanisms in several metastases from a melanoma patient undergoing immunotherapy. Cancer Immunol Immunother 56(1):88–94

    Article  PubMed  Google Scholar 

  • Mendez R, Rodriguez T, del Campo A, Monge E, Maleno I, Aptsiauri N, Jimenez P, Pedrinaci S, Pawelec G, Ruiz-Cabello F, Garrido F (2008) Characterization o f HLA class I altered phenotypes in a panel of human melanoma cell lines. Cancer Immunol Immunother 57:719–729

    Article  CAS  PubMed  Google Scholar 

  • Menon A, Tollenaar R, van de Velde CJ, Putter H, Janssen-Van Rhijn CM, Keijzer R, Fleuren GJ, Kuppen PJ (2004) p53 and HLA class I expression are not down regulated in colorectal cancer liver metastasis. Clin Exp Metastasis 21:79–85

    Article  CAS  PubMed  Google Scholar 

  • Mertens F, Johansson B, Husglund M, Mitelman F (1997) Chromosomal imbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Res 57:2765–2780

    CAS  PubMed  Google Scholar 

  • Metzelaar-Blok J, Jager M, Moghaddam PH, van der Slik A, Gighart M (1999) Frequent loss of heterozygosity on chromosome 6p in uveal melanoma. Hum Immunol 60:962–969

    Article  CAS  PubMed  Google Scholar 

  • Michael A, Pandha HS (2003) Renal-cell carcinoma: tumour markers, T-cell epitopes and potential for new therapies. Lancet Oncol 4:215–221

    Article  CAS  PubMed  Google Scholar 

  • Moller P, Herrmann B, Moldenhauer G, Momburg F (1987) Defective expression of MHC class I antigens is frequent in B-cell lymphomas of high-grade malignancy. Int J Cancer 40:32–39

    Article  CAS  PubMed  Google Scholar 

  • Moller P, Mattfeldt T, Gross C, Schlosshauer P, Koch A, Koretz K, Moldenhauer G, Kaufmann M, Otto HF (1989) Expression of HLA-A, B, C, DR, DP, DQ and HLA-D associated invariant chain (Li) in non-neoplastic mammary epithelium, fibroadenoma, adenoma and carcinoma of the breast. Am J Pathol 135:73–83

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moller P, Koretz K, Schlag P, Momburg F (1991) Frequency of abnormal expression of HLA A,B,C and HLA-DR molecules, invariant chain and LFA-3 (CD58) in colorectal carcinoma and its impact on tumor recurrence. Int J Cancer Suppl 6:155–162

    Article  CAS  PubMed  Google Scholar 

  • Momburg F, Koch S (1989) Selective loss of β2-microglobuline mRNA in human colon carcinoma. J Exp Med 169:309–314

    Article  CAS  PubMed  Google Scholar 

  • Momburg F, Degener T, Bacchus E, Moldenhauer G, Hammerling GJ, Moller P (1986a) Loss of HLA-A,B,C and de novo expression of HLA-D in colorectal cancer. Int J Cancer 37:179–184

    Article  CAS  PubMed  Google Scholar 

  • Momburg F, Moller P, Moldenhauer G, Hammerling G (1986b) Loss of HLA-A-B-C in colorectal carcinoma is related to the degree of differentiation. J Immunogenet 13:195–199

    Article  CAS  PubMed  Google Scholar 

  • Momburg F, Ziegler A, Harpprecht J et al (1989) Selective loss of HLA-A or HLA-B antigen expression in colon carcinoma. J Immunol 142:352–358

    CAS  PubMed  Google Scholar 

  • Montes P, Kerick M, Bernal M, Hernandez F, Jimenez P, Garrido P, Marquez A, Jurado M, Martin J, Garrido F, Ruiz-Cabello F (2018) Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients. Oncotarget 9(97):36929–36944

    Article  PubMed  PubMed Central  Google Scholar 

  • Moore M, Ghosh AK, Johnston D, Street AJ (1986) Expression of MHC class II products on human colorectal cancer: an immunohistological and flow cytometric study. J Immunogenet 13(2/3):201–209

    Article  CAS  PubMed  Google Scholar 

  • Moore M, Ghosh AK, Jones DJ (1989) MHC status of primary human colorectal carcinoma: biological significance and implications for host immune recognition. Acta Chir Scan Suppl 549:17–25

    CAS  Google Scholar 

  • Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette Guerin in the treatment of superficial bladder tumors. J Urol 116:180–183

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Bander NH, Nanus DM (1996) Renal cell carcinoma. N Engl J Med 335:865–876

    Article  CAS  PubMed  Google Scholar 

  • Muller M, Gounari F, Prifti S, Hacker HJ, Schirrmacher V, Khazaie K, Eblac Z (1998) Tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells. Cancer Res 58:5439–5446

    CAS  PubMed  Google Scholar 

  • Natali PG, Giacomini P, Bigotti A, Imai K, Nicotra MR, Ferrone S (1983a) Heterogeneity in the expression of HLA and tumor associated antigens by surgically removed and cultured breast carcinoma cells. Cancer Res. 43:660–668

    CAS  PubMed  Google Scholar 

  • Natali PG, Cavaliere R, Ferrone S (1983b) Antigenic heterogeneity of surgically removed primary and autologous metastatic melanoma lesions. J Immunol 130:1462–1467

    CAS  PubMed  Google Scholar 

  • Natali PG, Bigotti A, Nicotra MR, Viora M, Manfredi D, Ferrone S (1984) Distribution of human class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin. Cancer Res 44:4679–4687

    CAS  PubMed  Google Scholar 

  • Natali PG, Nicotra MR, Bigotti A, Venturo I, Marcenaro L, Giacomini P, Russo C (1989) Selective changes in expression of HLA class I polymorphic determinants in human solid tumors. Proc Natl Acad Sci USA 86(17):6719–6723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nie Y, Yang G, Song Y, Zhao X, So C, Liao J, Wang LD, Yang CS (2001) DNA hypermetilation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas. Carcinogenesis 22(10):1615–1623

    Article  CAS  PubMed  Google Scholar 

  • Nouri A, Smith M, Crosby D, Oliver RT (1990) Selective and non selective loss of immunoregulatory molecules (HLA-A,B,C antigens and LFA-3) in transitional cell carcinoma. Br J Cancer 62:603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nouri A, Hussain R, Oliver R (1994) The frequency of major histocompatibility complex antigen abnormalities in urological tumors and their corrections by gene transfection or cytokine stimulation. Cancer Gene Therapy 1(2):119–123

    CAS  PubMed  Google Scholar 

  • Ochsenbein AF, Klenerman P, Karrer U, Ludewig B, Pericin M, Hengartner H, Zinkernagel RM (1999) Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci USA 96:2233–2238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogino T, Shigyo H, Ishii H, Katayama A, Miyokawa N, Harabuchi Y, Ferrone S (2006) HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker. Cancer Res 66(18):9281–9289

    Article  CAS  PubMed  Google Scholar 

  • Pangault C, Amiot I, Caulet-Maugendre S, Brasseur F, Guilloux V, Drenou B, Faucher R, Onno M (1999) HLA-G protein expression is not induced during malignant transformation. Tissue Antigens 53:335–345

    Article  CAS  PubMed  Google Scholar 

  • Parham P, Barnstable CJ, Bodmer WF (1979) Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C antigens. J Immunol 123:324–328

    Google Scholar 

  • Paschen A, Mendez RM, Jimenez P, Sucker A, Ruiz-Cabello F, Song M, Garrido F, Schadendorf D (2003) Complete loss of HLA class I antigen expression on melanoma cells: a result of successive mutational events. Int J Cancer 103:759–767

    Article  CAS  PubMed  Google Scholar 

  • Paterson AC, Sciot R, Kew MC, Callea F, Dusheiko GM, Desmet VJ (1988) HLA expression in human hepatocellular carcinoma. Br J Cancer 57:369–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul P, Rouas-Freisss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal FA, Avril MF, Dausset J, Guillet JG, Carosella ED (1998) HLA-G expression in melanoma: A way for tumor cells to escape from immunesurveillance. Proc Natl Acad Sci 95:4510–4515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pazmany L, Mandelboim O, Valez-Gomez M, Davis DM, Reyburn HT, Strominger JL (1996) Protection from natural killer cell-mediated lysis by HLA-G expression on target cells. Science 274:792–795

    Article  CAS  PubMed  Google Scholar 

  • Pellegrino MA, Ferrone S, Reisfeld RA, Irie RF, Golub SH (1977) Expression of histocompatibility (HLA) antigens on tumor cells and normal cells from patients with melanoma. Cancer 40:36–41

    Article  CAS  PubMed  Google Scholar 

  • Peltenburg L, Schrier P (1994) Transcriptional suppression of HLA-B expression by c-Myc is mediated through the core promoter elements. Immunogenetics 40:54–61

    Article  CAS  PubMed  Google Scholar 

  • Pera E, Moreno A, Galindo L (1986) Prognostic factors in laryngeal carcinoma. A multifactorial study of 416 cases. Cancer 58:928–934

    Article  CAS  PubMed  Google Scholar 

  • Perea F, Bernal M, Sanchez-Palencia A, Carretero J, Torres C, Bayarri C, Gomez-Morales GF, Ruiz-Cabello F (2017) The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration. Int J Cancer 140:888–899

    Article  CAS  PubMed  Google Scholar 

  • Perea F, Sanchez-Palencia A, Gomez M, Bernal M, Concha A, Mendez Garcia M, Gonzalez-Ramirez R, Kerick M, Martin J, Garrido F, Ruiz-Cabello F, Aptsiauri N (2018) HLA class I loss and PD-L1 expression in lung cancer: impact on T cell-infiltration and immune escape. Oncotarget 9(3):4120–4133

    Article  PubMed  Google Scholar 

  • Perez M, Garrido A, Algarra I, Garrido F (1985) Different H-2 phenotypes in clones derived from a new BALB/c solid tumor. Its relevance for local tumor growth. Immunologia 4:60–69

    CAS  Google Scholar 

  • Perez M, Cabrera T, Lopez Nevot MA, Gomez M, Peran F, Ruiz-Cabello F, Garrido F (1986) Heterogeneity of the expression of class I and II HLA antigens in human breast carcinoma. J Immunogenet 13:247–253

    Article  CAS  PubMed  Google Scholar 

  • Perez M, Garrido A, Algarra I, Caballero A, Delgado C, Collado MD, Fernandez-Cruz E, Garrido F (1989) H-2 antigens and tumour associated transplantation antigens in clones derived from a methylcholantrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response. Exp Clin Immunogenet 6:204–218

    CAS  PubMed  Google Scholar 

  • Perez M, Algarra I, Ljunggren HG, Caballero A, Mialdea MJ, Gaforio JJ, Klein G, Karre K, Garrido F (1990) A weakly tumorigenic phenotype with high MHC class-I expression is associated with high metastatic potential after surgical removal of the primary murine fibrosarcoma.Int. J Cancer 46(2):258–261

    CAS  Google Scholar 

  • Perez B, Benitez R, Fernandez MA, Oliva MR, Soto JL, Lopez-Nevot MA, Garrido F (1999) A new β2 microglobulin mutation found in a melanoma tumor cell line. Tissue Antigens 53:569–572

    Article  CAS  PubMed  Google Scholar 

  • Perez-Ayala M, Ruiz-Cabello F, Esteban F, Concha A, Redondo M, Oliva MR, Cabrera T, Garrido F (1990) Presence of HPV 16 sequences in laryngeal carcinomas. Int J Cancer 46:8–11

    Article  CAS  PubMed  Google Scholar 

  • Polakova K, Krcova M, Kuba D, Russ G (2003) Analysis of HLA-G expression in malignant hematopoetic cells from leukemia patients. Leuk Res 27:643–648

    Article  CAS  PubMed  Google Scholar 

  • Porgador A, Brenner E, Vadai M, Feldman M, Eisenbach L (1991) Immunization by gamma-IFN-treated B16-F10.9 melanoma cells protects against metastatic spread of the parental tumor. Int J Cancer 6(Supplement):54–60

    Article  CAS  Google Scholar 

  • Rajagopalan S, Long E (1999) A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med 189(7):1093–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramal LM, Maleno I, Cabrera T, Collado A, Ferron A, Lopez-Nevot MA, Garrido F (2000a) Molecular strategies to define HLA haplotype loss in microdissected tumor cells. Hum Immunol 61:1001–1012

    Article  CAS  PubMed  Google Scholar 

  • Ramal LM, Feenstra M, Collado A, van der Zwan AW, Lopez-Nevot MA, Tilanus M, Garrido F (2000b) Criteria to define HLA haplotype loss in human solid tumors. Tissue Antigens 55:443–448

    Article  CAS  PubMed  Google Scholar 

  • Real LM, Jimenez P, Canton J, Kirkin A, Garcia A, Abril E, Zeuthen J, Ruiz-Cabello F, Garrido F (1998) In vivo and in vitro generation of a new altered HLA phenotype in melanoma tumor cell variants expressing a single HLA class I allele. Int J Cancer 75:317–323

    Article  CAS  PubMed  Google Scholar 

  • Real LM, Cabrera T, Collado A, Jimenez P, Garcia A, Ruiz-Cabello F, Garrido F (1999a) Expression of HLA-G in tumours is not a frequent event. Int J Cancer 81:512–518

    Article  CAS  PubMed  Google Scholar 

  • Real LM, Cabrera T, Canton J, Oliva R, Ruiz-Cabello F, Garrido F (1999b) Looking for HLA-G expression in human tumors. J Reprod Immunol 43:263–273

    Article  CAS  PubMed  Google Scholar 

  • Real LM, Jimenez P, Kirkin A, Serrano A, Garcia A, Canton J, Zeuthen J, Garrido F, Ruiz-Cabello F (2001) Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines derived from the same patient. Cancer Immunol Immunother 49:621–628

    Article  CAS  PubMed  Google Scholar 

  • Redondo M, Ruiz-Cabello F, Concha A, Cabrera T, Perez-Ayala M, Oliva MR, Garrido F (1991a) Altered HLA class I expression in non-small cell lung cancer is independent of c-myc alteration. Cancer Res 51:2463–2468

    CAS  PubMed  Google Scholar 

  • Redondo M, Concha A, Oldiviela R, Cueto A, Gonzalez A, Garrido F, Ruiz-Cabello F (1991b) Expression of HLA class I and II antigens in bronchogenic carcinomas: Its relationship to cellular DNA content and clinical-pathological parameters. Cancer Res 51:4948–4954

    CAS  PubMed  Google Scholar 

  • Redondo M, Concha A, Ruiz-Cabello F, Morell M, Esteban F, Talavera P, Garrido F (1997) Class I major histocompatibility complex antigens and tumor ploidy in breast and bronchogenic carcinomas. Cancer Detect Prev 21:22–28

    CAS  PubMed  Google Scholar 

  • Rees RC, Buckle A-M, Gelsthorpe K, James V, Polter CW, Rogers K, Jacob G (1988) Loss of polymorphic A and B locus HLA antigens in colon carcinoma. Br J Cancer 57:374–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rockett JC, Darnton SJ, Crocker J, Matthews HR, Morris AG (1995) Expression of HLA-ABC, HLA-DR and intercellular adhesion molecule-1 in oesophageal carcinoma. J Clin Pathol 48:539–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodolfo M, Luksch R, Stockert E, Chen YT, Collini P, Ranzani T, Lombardo C, Dalerba P, Rivoltini L, Arienti F et al (2003) Antigen-specific immunity in neuroblastoma patients: antibody and T cell recognition of NY-ESO-1 tumor antigen. Cancer Res 63:6948–6955

    CAS  PubMed  Google Scholar 

  • Rodriguez F, Peran F, Garrido F, Ruiz-Cabello F (1994) Upmodulation by estrogen of HLA class I expression in breast tumor cell lines. Immunogenetics 39:161–167

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez T, Mendez R, Roberts CH, Ruiz-Cabello F, Dodi IA, Lopez Nevot MA, Paco L, Maleno I, Marsh SG, Pawelec G, Garrido F (2005) High frequency of homozygosity of the HLA region in melanoma cell lines reveals a pattern compatible with extensive loss of heterozygosity. Cancer Immunol Immunother 54:141–148

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez T, Mendez R, Del Campo A, Jimenez P, Aptsiauri N, Garrido F, Ruiz-Cabello F (2007a) Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines. BMC Cancer 7:34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rodriguez T, Aptsiauri N, Mendez R, Jimenez P, Ruiz-Cabello F, Garrido F (2007b) Different mechanisms can lead to the same altered HLA class I phenotype in tumors. Tissue Antigens 69(Suppl 1):259–263

    Article  CAS  PubMed  Google Scholar 

  • Romero P, Coulie P (2014) Adaptive T-cell immunity and tumor antigen recognition. In: Rees RC (ed) Tumor immunology and immunotherapy. Oxford University Press, Oxford, pp 1–14

    Google Scholar 

  • Romero JM, Jimenez P, Cabrera T, Cozar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F (2005) Coordinated downregulation of the antigen presentation machinery and HLA class I/b2-microglobuline complex is responsible for HLA-ABC loss in bladder cancer. Int J Cancer 113:605–610

    Article  CAS  PubMed  Google Scholar 

  • Romero JM, Aptsiauri N, Vazquez F, Cozar JM, Canton J, Cabrera T, Tallada M, Garrido F, Ruiz-Cabello F (2006) Analysis of the expression of HLA class I, proinflamatory cytokines and chemokines in primary tumours from patients with localized and metastatic renal cell carcinoma. Tissue Antigen 68:303–310

    Article  CAS  Google Scholar 

  • Romero I, Martinez M, Garrido C, Collado A, Algarra I, Garrido I, Garcia-Lora A (2012) The tumour suppressor Fhit positively regulates MHC class I expression on cancer cells. J Pathol 227:367–379

    Article  CAS  PubMed  Google Scholar 

  • Romero I, Garrido C, Algarra I, Collado A, Garrido F, Garcia-Lora AM (2014a) T lymphocytes restrain spontaneous metastases in permanent dormancy. Cancer Res 74(7):1958–1968

    Article  CAS  PubMed  Google Scholar 

  • Romero I, Garrido F, Garcia-Lora AM (2014b) A novel preclinical murine model of immune-mediated metastatic dormancy. Oncoimmunology 3:e29258. ECollection 2014. Vol 9

    Article  PubMed  PubMed Central  Google Scholar 

  • Romero I, Garrido F, Garcia-Lora A (2014c) Metastases in immune-mediated dormancy: a new opportunity for targeting cancer. Cancer Res 74(23):6750–6757

    Article  CAS  PubMed  Google Scholar 

  • Romero I, Garrido C, Algarra I, Chamorro V, Collado A, Garrido F, Garcia-Lora A (2018) MHC intratumoral heterogeneity may predict cancer progression and response to immunotherapy. Front Immunol, article 112. https://doi.org/10.3389/fimmu.22018.00102

  • Rosa F, Berissi H, Weissenbach J, Maroteaux L, Fellous M, Revel M (1983) The β2-microglobuline mRNA in human Daudi cells has a mutated initiation codon but is still inducible by interferon. EMBO J 2:239–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruiter DJ, Bahn AK, Harrist TJ, Sober AJ, Mim MC (1982) Major histocompatibility antigens and mononuclear inflammatory infiltrate in benign nevomelanocytic proliferations and malignant melanoma. J Immunol 129:2808–2812

    CAS  PubMed  Google Scholar 

  • Ruiter DJ, Mattijssen V, Broecker EB, Ferrone S (1991) MHC antiegns in human melanomas. Semin Cancer Biol 2(1):35–45

    CAS  PubMed  Google Scholar 

  • Ruiz-Cabello F, Garrido F (2002) Tumor evasion of the immune system. In: Parmiani G, Lotze M (eds) Tumor immunology: molecular defined antigens and clinical applications. Taylor and Francis, New York, pp 177–203

    Google Scholar 

  • Ruiz-Cabello F, Ferron MA, Lopez-Nevot MA, Pedrinaci S, Conejo JM, Esteban F, Garrido F (1987) MHC class I antigen expression on human tumors. Histocompatibility Testing. In: Dupont B (ed) X international histocompatibility workshop, New York, p 473, November 1987

    Google Scholar 

  • Ruiz-Cabello F, Lopez-Nevot MA, Gutierrez J, Oliva MR, Romero C, Ferron A, Esteban F, Hueling C, Piris MA, Rivas C, Garrido F (1989) Phenotypic expression of histocompatibility antigens in human primary tumours and metastases. Clin Exp Metastasis 7:213–226

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Cabello F, Perez-Ayala M, Gomez O, Redondo M, Concha A, Cabrera T, Garrido F (1991a) Molecular analysis of MHC class I alterations in human tumour cell lines. Int J Cancer 6(Supplement):123–130

    Article  CAS  Google Scholar 

  • Ruiz-Cabello F, Klein E, Garrido F (1991b) MHC antigens in human tumours. Immunol Lett 29:181–189

    Article  CAS  PubMed  Google Scholar 

  • Ryschich E, Cebotari O, Fabian OV, Autschbach F, Kleeff J, Friess H, Bierhaus A, Buchler MW, Schmidt J (2004) Loss of heterozygosity in the HLA class I region in human pancreatic cancer. Tissue Antigens 64:696–702

    Article  CAS  PubMed  Google Scholar 

  • Ryschich E, Notzel T, Hinz U, Autschbach F, Ferguson J, Simon I, Weitz J, Frohlich B, Klar E, Buchler M, Schmidt J (2005) Control of T cell mediated immune response by HLA class I in human pancreatic carcinoma. Clin Cancer Res 11:498–504

    CAS  PubMed  Google Scholar 

  • Saenz-Lopez P, Gouttefangeas C, Hennenlotter A, Concha A, Maleno I, Ruiz-Cabello F, Cozar JM, Tallada M, Stenzl A, Rammensee HG, Garrido F, Cabrera T (2010) Higher HLA class I expression in renal cell carcinoma than in autologous normal tissue. Tissue Antigen 75:110–118

    Article  CAS  Google Scholar 

  • Sagalowsky AI, Molberg K (1999) Solitary metastasis of renal cell carcinoma to the contralateral adrenal gland 22 years after nephrectomy. Urology 54:162

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T (2001) Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity and transplantation tolerance. Immunol. Rev. 182:18–32

    Article  CAS  PubMed  Google Scholar 

  • Salgado R, Denker C, Demaria S, Sitaine N, Klauschen F, Pruneri G, Wiener S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richarson AL et al (2015) The evaluation of tumour infiltrating lymphocytes (TILs) in breast cancer: recommendations by an international TILs working group 2014. Ann Oncol 26:259–271

    Article  CAS  PubMed  Google Scholar 

  • Sanda MG, Restifo NP, Walsh JC, Kawakami Y, Nelson WG, Pardoll DM, Simons JW (1995) Molecular characterization of defective antigen processing in human prostate cancer. J Nat Cancer Inst 87:280–285

    Article  CAS  PubMed  Google Scholar 

  • Sarkar AK, Nuchtern JG (2000) Lysis of MYCN- amplified neuroblastoma cells by MYCN peptide-specific cytotoxic T lymphocytes. Cancer Res 60:1908–1913

    CAS  PubMed  Google Scholar 

  • Schrier P, Versteeg R, Peltenburg LT, Plomp AC, Van’t Veer LJ, Kruse-Wolters KM (1991) Sensitivity of melanoma cells lines to natural killer cells: a role for oncogene-modulated HLA class I expression ? Semin Cancer Biol 2(1):73–83

    CAS  PubMed  Google Scholar 

  • Schultze JL, Nadler LM (2003) Lack of sufficient B7 expression as a tumor escape mechanism: implications for immunotherapy. In: Ochoa AC (ed) Mechanisms of tumor escape from the immune response. Taylor & Francis, London, pp 66–93

    Google Scholar 

  • Scupoly MT, Sartoris S, Tosi G, Ennas MG, Nicolis M, Cestari T, Zamboni G, Martignoni G, Lemoine NR, Scarpa A, Accolla RS (1996) Expression of MHC class I and class II antigens in pancreatic adenocarcinomas. Tissue Antigens 48:301–311

    Article  Google Scholar 

  • Seliger B (2012) Novel insights into the molecular mechanisms of HLA class I abnormalities. Cancer Immunol Immunother 61:249–254

    Article  CAS  PubMed  Google Scholar 

  • Seliger B, Maeurer MJ, Ferrone S (2000) Antigen-processing machinery breakdown and tumor growth. Immunol Today 21(9):455–464

    Article  CAS  PubMed  Google Scholar 

  • Seliger B, Ritz U, Abele R, Bock M, Tampe R, Sutter G, Drexler I, Huber C, Ferrone S (2001) Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway. Cancer Res. 61:8647–8650

    CAS  PubMed  Google Scholar 

  • Seliger B, Cabrera T, Garrido F, Ferrone F (2002) HLA class I antigen abnormalities and immune escape by malignant cells. Semin Cancer Biol 12:3–13

    Article  CAS  PubMed  Google Scholar 

  • Seliger B, Ruiz-Cabello F, Garrido F (2008) IFN inducibility of major histocompatibility antigens in tumors. Adv Cancer Res 101:249–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano A, Brady CS, Jimenez P, Duggan-Keen MF, Mendez R, Stern P, Garrido F, Ruiz-Cabello F (2000) A mutation determining the loss of HLA-A2 antigen expression in a cervical carcinoma reveals novel splicing of human MHC class I classical transcripts in both tumoral and normal cells. Immunogenetics 51:1047–1052

    Article  CAS  PubMed  Google Scholar 

  • Serrano A, Tanzarella S, Lionello I, Mendez R, Traversari C, Ruiz-Cabello F, Garrido F (2001) Reexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-20-deoxycytidine treatment. Int J Cancer 94:243–251

    Article  CAS  PubMed  Google Scholar 

  • Sharpe JC, Abel PD, Gilbertson JA, Brawn P, Foster CS (1994) Modulated expression of human leucocyte antigen class I and class II determinants in hyperplastic and malignant human prostatic epithelium. Br J Urol 74:609–616

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Zhag J, Miao F, Zhang J, Jiang Q, Chen H, Shan X, Wie W (2005) Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer. World J Gastroenterol 11(23):3628–3631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheu J, Shih I (2007) Clinical and biological significance of HLA-G expression in ovarian cancer. Semin Cancer Biol 17(6):436–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singal DP, Ye M, Bienzle D (1998) Transfection of TAP1 genes restores HLA class I expression in human small-cell lung carcinoma. Int J Cancer 75(1):112–116

    Article  CAS  PubMed  Google Scholar 

  • Smith MEF, Bodmer W, Bodmer J (1988) Selective loss of HLA-A,B,C locus products in colorectal adenocarcinoma. Lancet 1:823–824

    Article  CAS  PubMed  Google Scholar 

  • Smith MEF, Marsch SGE, Bodmer J, Gelsthorpe K, Bodmer W (1989) Loss of HLA-A,B,C allele products and lymphocyte-function-associated antigen 3 in colorectal neoplasia. Proc Natl Acad Sci (Washington) 86:5557–5561

    Article  CAS  Google Scholar 

  • So T, Takenoyama M, Mizukami M, Ichiki Y, Sugaya M, Hanagiri T, Sugio K, Yasumoto K (2005) Haplotype loss of HLA class I antigens as an escape mechanism from immune attack in lung cancer. Cancer Res 65(13):5945–5952

    Article  CAS  PubMed  Google Scholar 

  • Soling A, Schurr P, Berthold F (1999) Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma. Anticancer Res 19:2205–2209

    CAS  PubMed  Google Scholar 

  • Soong TW, Hui KM (1992) Locus-specific transcriptional control of HLA genes. J Immunol 149(6):2008–2020

    CAS  PubMed  Google Scholar 

  • Stern P (1996) Immunity to human Papilloma virus-associated cervical neoplasia. Adv Cancer Res 69:175–211

    Article  CAS  PubMed  Google Scholar 

  • Sucker A, Zhao F, Pieper N, Heeke C, Maltaner R, Stadtler N, Real B, Bielefeld N, Howe S, Weide B, Gutzmer R, Utikal J, Loquai C, Gogas H, Klein-Hitpass L, Zeschnigk M, Westendorf A, Trilling M, Horn S, Schilling B, Schadendorf D, Griewank K, Paschen A (2017) Adquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistance melanoma lesions. Nat Commun 8:15440. https://doi.org/10.1038/ncomms15440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugimoto T, Horii Y, Hino T, Kemshead JT, Kuroda H, Sawada T, Morioka H, Imanishi J, Inoko H (1989) Differential susceptibility of HLA class II antigens induced by gamma-interferon in human neuroblastoma cell lines. Cancer Res 49:1824–1828

    CAS  PubMed  Google Scholar 

  • Terabe M, Berzofsky JA (2004) Immunoregulatory T cells in tumor immunity. Curr Opin Immunol 16(2):157–162

    Article  CAS  PubMed  Google Scholar 

  • Thomas L (1959) In: Lawrence HS (ed) Discussion of cellular and humoral aspects of the hypersensitivity states. Hoeber-Harper, New York, pp 529–532

    Google Scholar 

  • Tomita Y, Matsumoto Y, Nishiyama T, Fujiwara M (1990) Reduction of major histocompatibility complex class I antigens on invasive carcinoma and high-grade transitional cell carcinoma. J Pathol 162:157–164

    Article  CAS  PubMed  Google Scholar 

  • Torres LM, Cabrera T, Concha A, Oliva MR, Ruiz-Cabello F, Garrido F (1993) HLA class I expression and HPV-16 sequences in premalignant and malignant lesions of the cervix. Tissue Antigens 41:65–71

    Article  CAS  PubMed  Google Scholar 

  • Torres MJ, Ruiz-Cabello F, Skoudy A, Berrozpe G, Jimenez P, Serrano A, Real FX, Garrido F (1996) Loss of an HLA haplotype in pancreas cancer tissue and its corresponding tumor derived cell line. Tissue Antigens 47:372–381

    Article  CAS  PubMed  Google Scholar 

  • Tsioulias G, Triadafilopoulos G, Goldin E, Papavassiliou ED, Rizos S, Bassioukas P, Rigas B (1993) Expression of HLA class I antigens in sporadic adenomas and histological normal mucosa of the colon. Cancer Res 53(10 Suppl):2374–2378

    CAS  PubMed  Google Scholar 

  • Turbitt ML, Mackie RM (1981) Loss of β2 microglobulin from the cell surface of cutaneous malignant and premalignant lesions. Br J Dermato 104:507–513

    Article  CAS  Google Scholar 

  • Ugolini S, Vivier E (2000) Regulation of T cell function by NK cell receptors for classical MHC class I molecules. Curr Opin Immunol 12:295–300

    Article  CAS  PubMed  Google Scholar 

  • Urosevic M, Kurrer MO, Kamarashev J, Mueller B, Weder W, Burg G, Stahel RA, Dummer R, Trojan A (2001) Human leukocyte antigen G up-regulation in lung cancer assocites with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production. Am J Pathol 159:817–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, Perreli B, Cosentino C, Torri F, Angius A, Forno B, Casucci B, Bernardi M, Peccatori J, Corti C, Bondanza A, Ferrari M, Rossini S, Roncarolo MG, Bordignon C, Bonini C, Ciceri F, Fleischhauer K (2009) Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 361:478–488

    Article  CAS  PubMed  Google Scholar 

  • Vago L, Toffalori C, Ciceri F, Fleischhauer K (2012) Genomic loss of mismatched human leucocyte antigen and leukemia immune escape from haploidentical graf-versus-leukemia. Semin Oncol 39(6):707–715

    Article  PubMed  Google Scholar 

  • Van der Bruggen P, Traversary C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolitic T lymphocytes on a human melanoma. Science 254:1643–1647

    Article  PubMed  Google Scholar 

  • Van Duinen SG, Mauw BJ, de Graaff-Reitsma CB, Ruiter DJ (1984) Immunoelectron microscopic methods for demonstration of antigens on normal melanocytes and other epidermal cells. Lab Invest 50:733–741

    PubMed  Google Scholar 

  • Van’t Veer LJ, Beijersbergen RL, Bernards R (1993) N-myc suppresses major histocompatibility complex class I gene expression throught down-regulation of the p50 subunit of NF-kappa B. EMBO J 12:195–200

    Article  Google Scholar 

  • Verheyden S, Ferrone S, Mulder A, Claas FH, Schots R, De Moerloose B, Benoit Y, Demanet C (2009) Role of the inhibitory KIR ligand HLA-Bw4 and HLA-C expression levels in the recognition of leukemic cells by Natural Killer cells. Cancer Immunol Immunother 58(6):855–865

    Article  CAS  PubMed  Google Scholar 

  • Versteeg R, Kruse-Wlters M, Plomp A, Van Leeuwen A, Stam N, Ploegh H, Ruiter D, Schrier P (1989) Supression of class I human histocompatibility leukocyte antigen by c-myc is locus specific. J Exp Med 170:621–635

    Article  CAS  PubMed  Google Scholar 

  • Villalobos I, Takahashi Y, Akatsuka Y, Muramatsu H, Nishio N, Hama A, Yagasaki H, Saji H, Kato M, Ogawa S, Kojima S (2010) Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. Blood 115:3158–3161

    Article  CAS  PubMed  Google Scholar 

  • Villunger A, Strasser A (1999) The great escape: is immune evasion required for tumor progression? Nat Med 5:874–875

    Article  CAS  PubMed  Google Scholar 

  • Vitale M, Rezzani R, Rodella L, Zauli G, Grigolato P, Cadei M, Hicklin DJ, Ferrone F (1998) HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res 15(4):737–742

    Google Scholar 

  • Vitale M, Pelusi G, Taroni B, Gobbi G, Micheloni C, Rezzani R, Donato F, Wang X, Ferrone S (2005) HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage. Clin Cancer Res 11:67–72

    CAS  PubMed  Google Scholar 

  • Vokes EE, Weichselbaum RR, Lippman SM, Hong WK (1993) Head and neck cancer. N Engl J Med 328:184–194

    Article  CAS  PubMed  Google Scholar 

  • Volgelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    Article  Google Scholar 

  • Wadee A, Paterson A, Coplan KA, Reddy G (1994) HLA expression in hepatocellular carcinoma cell lines. Clin Exp Immunol 97:328–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meier CJ, Muñoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer wordwide. J Pathol 189:12–19

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Cao Y, Albino AP, Zeff RA, Houghton A, Ferrone S (1993) Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in β2-microglobuline messenger RNA. J Clin Invest 91(2):684–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Seliger B, Mike N, Momburg F, Knuth A, Ferrone S (1998) Molecular analysis of the HLA-A2 antigen loss by melanoma cells SK-MEL-29.1.22 and SK-MEL- 29.1.29. Cancer Res 58:2149–2157

    CAS  PubMed  Google Scholar 

  • Wang Z, Marincola FM, Rivoltini L, Parmiani G, Ferrone S (1999) Selective histocompatibility leukocyte antigen (HLA-A2) loss caused by aberrant pre-mRNA splicing in 624MEL28 melanoma cells J. Exp Med 190:205–215

    Article  CAS  Google Scholar 

  • Watson NF, Ramage JM, Madjd Z, Spendlove I, Ellis IO, Scholefield JH, Durrant LG (2006) Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. Int J Cancer 118:6–10

    Article  CAS  PubMed  Google Scholar 

  • Whelan JP, Chatten J, Lampson LA (1985) HLA class I and β2-microglobuline expression in frozen and formaldehyde-fixed paraffin sections of neuroblastoma tumors. Cancer Res 45:5976–5983

    CAS  PubMed  Google Scholar 

  • Whitwell HL, Hughes HPA, Moore M, Ahmed A (1984) Expression of major histocompatibility antigens and leucocyte infiltration in bening and malignant human breast disease. Br J Cancer 49:161–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson BS, Indiveri F, Pellegrino MA, Ferrone S (1979) DR (Ia-like) antigens on human melanoma cells. J Exp Med 149:658–668

    Article  CAS  PubMed  Google Scholar 

  • Winchester RJ, Wange CY, Gibovsky A, Kunkel HG, Lloyd KO, Old LJ (1978) Expression of Ia-like antigens on cultured human malignant melanoma cell lines. Proc Natl Acad Sci USA 75:6235–6241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wintzer HO, Benzing M, von Kleist S (1990) Lacking prognostic significance of beta 2 microglobuline, MHC class I and II antigen expression in breast carcinomas. Br J Cancer 62:289–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witjes JA, Umbas R, Debruine FM, Shalken JA (1995) Expression of markers for transitional cell carcinoma in normal bladder mucosa of patients with bladder cancer. J Urol 154:2185–2189

    Article  CAS  PubMed  Google Scholar 

  • Wölf M, Jungbluth A, Garrido F, Cabrera T, Meyen-Southard S, Spitz R, Ernestus K, Berthold F (2005) Expression of MHC class I, MHC class II and cancer germ line antigens in neuroblastoma. Cancer Immunol Immunother 54:400–406

    Article  CAS  Google Scholar 

  • Xia M, Zhang QJ, ShenYQ XLH, Chen FQ, Miao FQ, Wie W (2007) Concordant expression of proto-oncogene promyelocytic leukemia and major histocompatibility antigen HLA class I in human hepatocellular carcinoma. Tissue Antigens 70:272–282

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Zhang J, Miao F, Wei J, Shen C, Shen Y, Xie W (2008) Loss of heterozygosity at 6p21 underling HLA class I downregulation in Chinese primary esophageal squamous cell carcinomas 72:105–114

    Google Scholar 

  • Yang I, Tihan T, Han SJ, Wrensch MR, Wienke J, Sughrue ME, Parsa AT (2010) CD8+ T cell infiltrate in newly diagnose glioblastoma is associated with long-term survival. J Clin Neurosc 17:1381–1385

    Article  Google Scholar 

  • Yeung J, Hamilton R, Ohnishi K, Ikeura M, Potter D, Nikiforova M, Ferrone S, Jakacki R, Pollack I, Okada H (2013) LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma. Clin Cancer Res 19(7):1816–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshihama S, Roszik J, Downs I, Meissner T, Vijayan S, Chapuy B, Sidiq T, Shipp M, Lizee G, Kobayashi K (2016) NLRC5/MHC class I transactivator is a target for immune evasión in cancer. PNAS 113:5999–6004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeidman I (1957) Metastasis: a review of recent advances. Cancer Res 17:157–162

    CAS  PubMed  Google Scholar 

  • Zhang H, Melamed J, Wei P, Cox K, Frankel W, Bahnson RR, Robinson N, Pyka R, Liu Y, Zheng P (2003) Concordant down-regulation of protooncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer. Cancer Immunol 3:2–11

    Google Scholar 

  • Zhang Y, Yu S, Han Y, Wang Y, Sun Y (2018) Human leukocyte antigen-G expression and polymorphisms promote cancer development and guide cancer diagnosis/treatment. Oncol Lett 15:699–709

    PubMed  Google Scholar 

  • Zia A, Schildberg FW, Funke I (2001) MHC negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0Mo breast cancer patients. Int J Cancer 93:566–570

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Garrido, F. (2019). MHC/HLA Class I Loss in Cancer Cells. In: MHC Class-I Loss and Cancer Immune Escape. Advances in Experimental Medicine and Biology, vol 1151. Springer, Cham. https://doi.org/10.1007/978-3-030-17864-2_2

Download citation

Publish with us

Policies and ethics