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T cells in tumor microenvironment

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Tumor Biology

Abstract

Tumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called “tumor microenvironment” and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient’s outcome.

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References

  1. Ding Z-Y, Zou X-L, Wei Y-Q. Cancer microenvironment and cancer vaccine. Cancer Microenviron. 2012;5(3):333–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Buhrmann C, Kraehe P, Lueders C, Shayan P, Goel A, Shakibaei M. Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT. PLoS One. 2014;9(9), e107514.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schiavoni G, Gabriele L, Mattei F. The tumor microenvironment: a pitch for multiple players. Front Oncol. 2013;3:90.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mao Y, Keller ET, Garfield DH, Shen K, Wang J. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 2013;32(1–2):303–15.

    Article  PubMed  PubMed Central  Google Scholar 

  5. De Wever O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol. 2003;200(4):429–47.

    Article  PubMed  Google Scholar 

  6. Yhang ZZ, Ansell SM. The tumor microenvironment in follicular lymphoma. Clin Adv Hematol Oncol. 2012;10(12):810–8.

    Google Scholar 

  7. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432(7015):332–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    Article  CAS  PubMed  Google Scholar 

  9. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411(6835):375–9.

    Article  CAS  PubMed  Google Scholar 

  10. Crawford Y, Kasman I, Yu L, Zhong C, Wu X, Modrusan Z, et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell. 2009;15(1):21–34.

    Article  CAS  PubMed  Google Scholar 

  11. Tsellou E, Kiaris H. Fibroblast independency in tumors: implications in cancer therapy. Future Oncol. 2008;4(3):427–32.

    Article  PubMed  Google Scholar 

  12. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.

    Article  CAS  PubMed  Google Scholar 

  13. Aikawa T, Gunn J, Spong SM, Klaus SJ, Korc M. Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther. 2006;5(5):1108–16.

    Article  CAS  PubMed  Google Scholar 

  14. Chen CA, Ho CM, Chang MC, Sun WZ, Chen YL, Chiang YC, et al. Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor angiogenesis. Mol Ther. 2010;18(6):1233–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kurts C, Robinson BW, Knolle PA. Cross-priming in health and disease. Nat Rev Immunol. 2010;10(6):403–14.

    Article  CAS  PubMed  Google Scholar 

  16. Clausen J, Vergeiner B, Enk M, Petzer AL, Gastl G, Gunsilius E. Functional significance of the activation-associated receptors CD25 and CD69 on human NK-cells and NK-like T-cells. Immunobiology. 2003;207(2):85–93.

    Article  CAS  PubMed  Google Scholar 

  17. Lakshmikanth T, Burke S, Ali TH, Kimpfler S, Ursini F, Ruggeri L, et al. NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest. 2009;119(5):1251–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chan CJ, Andrews DM, McLaughlin NM, Yagita H, Gilfillan S, Colonna M. DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. J Immunol. 2010;184(2):902–11.

    Article  CAS  PubMed  Google Scholar 

  19. Moretta A. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol. 2002;2(12):957–64.

    Article  CAS  PubMed  Google Scholar 

  20. Moretta L, Ferlazzo G, Bottino C, Vitale M, Pende D, Mingari MC, et al. Effector and regulatory events during natural killer-dendritic cell interactions. Immunol Rev. 2006;214:219–28.

    Article  CAS  PubMed  Google Scholar 

  21. Morandi B, Mortara L, Chiossone L, Accolla RS, Mingari MC, Moretta L, et al. Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response. PLoS One. 2012;7(6), e39170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Barkan D, Green E, Chambers AF. Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur J Cancer. 2010;46(7):1181–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.

    Article  CAS  PubMed  Google Scholar 

  24. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14:1014–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Huang Y, Ma C, Zhang Q, Ye J, Wang F, Zhang Y, et al. CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome. Oncotarget. 2015.

  26. Ward PL, Koeppen HK, Hurteau T, Rowley DA, Schreiber H. Major histocompatibility complex class I and unique antigen expression by murine tumors that escaped from CD8+ T-cell-dependent surveillance. Cancer Res. 1990;50(13):3851–8.

    CAS  PubMed  Google Scholar 

  27. Yusuf N, Nasti TH, Katiyar SK, Jacobs MK, Seibert MD, Ginsburg AC. Antagonistic roles of CD4+ and CD8+ T-cells in 7,12-dimethylbenz(a)anthracene cutaneous carcinogenesis. Cancer Res. 2008;68(10):3924–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Eyles J, Puaux AL, Wang X, Toh B, Prakash C, Hong M, et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest. 2010;120(6):2030–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Clark Jr WH, Elder DE, Guerry 4th D, Braitman LE, Trock BJ, Schultz D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989;81(24):1893–904.

    Article  PubMed  Google Scholar 

  30. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998;58(16):3491–4.

    CAS  PubMed  Google Scholar 

  31. Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–13.

    Article  CAS  PubMed  Google Scholar 

  33. Pages F, Berger A, Camus M, Sanches-Cabo F, Costes A, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353:2654–66.

    Article  CAS  PubMed  Google Scholar 

  34. Senovilla L, Vacchelli E, Galon J, Adjemian S, Eggermont A, Fridman WH, et al. Trial watch: prognostic and predictive value of immune infiltrate in cancer. Oncoimmunology. 2012;1(8):1323–43.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mempel TR, Bauer CA. Intravital imaging of CD8+ T cell function in cancer. Clin Exp Metastasis. 2009;26(4):311–27.

    Article  PubMed  Google Scholar 

  36. Seder RA, Paul WE. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–73.

    Article  CAS  PubMed  Google Scholar 

  37. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med. 1998;188:2357–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stuehr DJ, Nathan CF. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med. 1989;169:1543–55.

    Article  CAS  PubMed  Google Scholar 

  39. Weiss JM, Ridnour LA, Back T, Hussain SP, He P, Maciag AE, et al. Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy. J Exp Med. 2010;207:2455–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kapsenberg ML, Hilkens CM, Wierenga EA, Kalinski P. The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy. Clin Exp Allergy. 1999;29 suppl 2:33–6.

    Article  PubMed  Google Scholar 

  41. Pereira MC, Oliveira DT, Kowalski LP. The role of eosinophils and eosinophil cationic protein in oral cancer: a review. Arch Oral Biol. 2011;56:353–8.

    Article  CAS  PubMed  Google Scholar 

  42. Bailey SR, Nelson MH, Himes RA, Li Z, Mehrota S, Paulos CM. Th17 cells in cancer: the ultimate identity crisis. Front Immunol. 2014;5:276.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Chamoto K, Kosaka A, Tsuji T, Matsuzaki J, Sato T, Takeshima T, et al. Critical role of the Th1/Tc1 circuit for the generation of tumor-specific CTL during tumor eradication in vivo by Th1-cell therapy. Cancer Sci. 2003;94(10):924–8.

    Article  CAS  PubMed  Google Scholar 

  44. Antony PA, Restifo NP. CD4+ CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2. J Immunother. 2005;28(2):120–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wilke CM, Wei S, Wang, Kryczek I, Fang J, Wang G, et al. T cell and antigen-presenting cell subsets in the tumor microenvironment. Cancer Immunol Immunother. 2013. doi:10.1007/978-1-4614.

    Google Scholar 

  46. Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, Ansell SM. Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin’s lymphoma. Cancer Res. 2009;69:5522–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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    Authors and Affiliations

    1. Department of Molecular Biology and Genetics, Molecular Immunology and Gene Regulation Laboratory, Izmir Institute of Technology, Urla, 35430, İzmir, Turkey

      Yağmur Kiraz, Yusuf Baran & Ayten Nalbant

    2. Faculty of Life and Natural Sciences, Abdullah Gul University, 38080, Kayseri, Turkey

      Yağmur Kiraz & Yusuf Baran

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    1. Yağmur Kiraz
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    Correspondence to Ayten Nalbant.

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    Conflict of interest

    The authors do not have any kind of conflict of interest affecting the compilation of the current knowledge in this area for writing this review. They apologize to the ones whose elegant studies are not included here because of space limitations.

    Funding

    Research in the corresponding author’s laboratory is in the Th17 T cell differentiation and immune regulation area and supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK) (Grant numbers 110T412 and 113Z362 to Dr. Ayten Nalbant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Yağmur Kiraz, Yusuf Baran and Ayten Nalbant contributed equally to this work.

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    Kiraz, Y., Baran, Y. & Nalbant, A. T cells in tumor microenvironment. Tumor Biol. 37, 39–45 (2016). https://doi.org/10.1007/s13277-015-4241-1

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    • DOI: https://doi.org/10.1007/s13277-015-4241-1

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