Skip to main content
SpringerLink
Log in

Immune check-point in endometrial cancer

  • Review Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Endometrial cancer (EC) is one of the most frequent tumors in women. Despite recent advances in treatment approaches, the prognosis in advanced, recurrent, or metastatic disease remains poor. The aim was to provide the clinician with an update, the current status, and the new developments in the management of EC. Based on the new EC molecular classification, we focused on the impact of immune check-point inhibitors.

Methods

Pivotal trials, published literature, and conference proceedings were reviewed. PubMed and Scopus databases were searched to select English-language articles.

Results

Immune check-point inhibitors are the subject of ongoing studies and their benefit seems to be related to microsatellite instability (MSI) status.

Conclusions

Immune check-point inhibitors should be considered a promising treatment option to better personalize therapeutic strategies in EC.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108

    Article  PubMed  Google Scholar 

  2. National Comprehensive Cancer Network (NCCN) guidelines. Uterine Neoplasms, Version 2.2019. https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf

  3. Dowdy SC (2014) Improving oncologic outcomes for women with endometrial cancer: realigning our sights. Gynecol Oncol 133(2):370–374

    Article  PubMed  PubMed Central  Google Scholar 

  4. De Felice F, Marchetti C, Palaia I (2015) Immunotherapy of ovarian cancer: the role of checkpoint inhibitors. J Immunol Res. 2015:191832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. De Felice F, Marchetti C, Palaia I (2018) Immune check-point in cervical cancer. Crit Rev Oncol Hematol 129:40–43

    Article  PubMed  Google Scholar 

  6. Longoria TC, Eskander RN (2015) Immunotherapy in endometrial cancer—an evolving therapeutic paradigm. Gynecol Oncol Res Pract 2:11

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wira CR, Fahey JV, Ghosh M (2010) Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 63(6):544–565

    Article  CAS  PubMed  Google Scholar 

  8. Vanderstraeten A, Tuyaerts S, Amant F (2015) The immune system in the normal endometrium and implications for endometrial cancer development. J Reprod Immunol 109:7–16

    Article  CAS  PubMed  Google Scholar 

  9. Vanderstraeten A, Luyten C, Verbist G (2014) Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy. Cancer Immunol Immunother 63(6):545–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lax SF, Kurman RJ (1997) A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verh Dtsch Ges Pathol 81:228–232

    CAS  PubMed  Google Scholar 

  12. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497(7447):67–73

    Article  CAS  Google Scholar 

  13. Le Gallo M, Bell DW (2014) The emerging genomic landscape of endometrial cancer. Clin Chem 60(1):98–110

    Article  CAS  PubMed  Google Scholar 

  14. Richman S (2015) Deficient mismatch repair: read all about it (review). Int J Oncol 47(4):1189–1202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gargiulo P, Della Pepa C, Berardi S (2016) Tumor genotype and immune microenvironment in POLE-ultramutated and MSI-hypermutated endometrial cancers: new candidates for checkpoint blockade immunotherapy? Cancer Treat Rev 48:61–68

    Article  CAS  PubMed  Google Scholar 

  16. De Felice F, Marchetti C, Boccia SM (2017) Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: an evidence-based approach on what women should know. Cancer Treat Rev 61:1–5

    Article  CAS  PubMed  Google Scholar 

  17. Kato M, Takano M, Miyamoto M (2015) DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers. J Gynecol Oncol 26(1):40–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Terada KY, Black M, Terada LH (2013) Survival of endometrial cancer patients with lymphatic invasion and deficient mismatch repair expression. Gynecol Oncol 129(1):188–192

    Article  CAS  PubMed  Google Scholar 

  19. Resnick KE, Frankel WL, Morrison CD (2010) Mismatch repair status and outcomes after adjuvant therapy in patients with surgically staged endometrial cancer. Gynecol Oncol 117(2):234–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shih KK, Garg K, Levine DA (2011) Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40 years of age and younger. Gynecol Oncol 123(1):88–94

    Article  CAS  PubMed  Google Scholar 

  21. Garg K, Shih K, Barakat R (2009) Endometrial carcinomas in women aged 40 years and younger: tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset. Am J Surg Pathol 33(12):1869–1877

    Article  PubMed  Google Scholar 

  22. Ruiz I, Martín-Arruti M, Lopez-Lopez E (2014) Lack of association between deficient mismatch repair expression and outcome in endometrial carcinomas of the endometrioid type. Gynecol Oncol 134(1):20–23

    Article  CAS  PubMed  Google Scholar 

  23. Basil JB, Goodfellow PJ, Rader JS (2000) Clinical significance of microsatellite instability in endometrial carcinoma. Cancer 89(8):1758–1764

    Article  CAS  PubMed  Google Scholar 

  24. Diaz-Padilla I, Romero N, Amir E (2013) Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol 88(1):154–167

    Article  PubMed  Google Scholar 

  25. Howitt BE, Shukla SA, Sholl LM (2015) Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol 1(9):1319–1323

    Article  PubMed  Google Scholar 

  26. Le DT, Uram JN, Wang H (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mehnert JM, Panda A, Zhong H (2016) Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest 126(6):2334–2340

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ott PA, Bang YJ, Berton-Rigaud D (2017) Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 35(22):2535–2541

    Article  CAS  PubMed  Google Scholar 

  29. Makker V, Rasco DW, Dutcus CE (2017) A phase Ib/II trial of lenvatinib (LEN) plus pembrolizumab (Pembro) in patients (Pts) with endometrial carcinoma. J Clin Oncol. 35(15):5598–5598

    Article  Google Scholar 

  30. Fleming GF, Emens LA, Eder JP (2017) Clinical activity, safety and biomarker results from a phase Ia study of atezolizumab (atezo) in advanced/recurrent endometrial cancer (rEC). J Clin Oncol 35(15):5585

    Article  Google Scholar 

  31. Merck and Co., Inc. 2014. Keytruda (Pembrolizumab) package insert. Whitehouse Station, NJ. http://bit.ly/2cTmItE

  32. La-Beck NM, Jean GW, Huynh C (2015) Immune checkpoint inhibitors: new insights and current place in cancer therapy. Pharmacotherapy 35(10):963–976

    Article  CAS  PubMed  Google Scholar 

  33. https://clinicaltrials.gov/ct2/show/NCT02628067

  34. https://clinicaltrials.gov/ct2/show/NCT01876511

  35. https://clinicaltrials.gov/ct2/show/NCT02728830

  36. https://clinicaltrials.gov/ct2/show/NCT02630823

  37. https://clinicaltrials.gov/ct2/show/NCT02549209

  38. https://clinicaltrials.gov/ct2/show/NCT02912572

  39. https://clinicaltrials.gov/ct2/show/NCT02899793

  40. https://clinicaltrials.gov/ct2/show/NCT02501096

  41. https://clinicaltrials.gov/ct2/show/NCT02646748

  42. https://clinicaltrials.gov/ct2/show/NCT03015129

  43. https://clinicaltrials.gov/ct2/show/NCT02982486

  44. https://clinicaltrials.gov/ct2/show/NCT03310567

  45. https://clinicaltrials.gov/ct2/show/NCT03276013

  46. https://clinicaltrials.gov/ct2/show/NCT03517449

  47. https://clinicaltrials.gov/ct2/show/NCT03192059

  48. https://clinicaltrials.gov/ct2/show/NCT02178722

  49. https://clinicaltrials.gov/ct2/show/NCT02914470

  50. https://clinicaltrials.gov/ct2/show/NCT02423954

Download references

Author information

Authors and Affiliations

  1. Department of Radiotherapy, Policlinico Umberto I “Sapienza” University of Rome, Viale Regina Elena 326, 00161, Rome, Italy

    Francesca De Felice & Vincenzo Tombolini

  2. Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli—IRCCS, Rome, Italy

    Claudia Marchetti

  3. Department of Gynecological, Obstetrical Sciences and Urological Sciences “Sapienza” University of Rome, Rome, Italy

    P. Benedetti Panici

Authors
  1. Francesca De Felice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudia Marchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Tombolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Benedetti Panici
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesca De Felice.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Felice, F., Marchetti, C., Tombolini, V. et al. Immune check-point in endometrial cancer. Int J Clin Oncol 24, 910–916 (2019). https://doi.org/10.1007/s10147-019-01437-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-019-01437-7

Keywords

Search

Navigation