Immune сheckpoint inhibitors in ovarian cancer

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The review considers modern immunotherapy for ovarian cancer with immune checkpoint inhibitors that interfere with the ability of the tumor to activate control proteins on the surface of T-cells, preventing cancer from evading the immune response and allowing the immune system to generate an antitumor response. The presence of spontaneous tumor-specific T-cells in cancer patients is a factor in creating ways to overcome the blockade of the immune system's ability to inactivate tumor cells. The use of immunotherapy with monoclonal antibodies makes it possible to influence the checkpoints of immunity, leads to the activation of the immune response, blocking the interaction of the PD-1 protein with the corresponding PD-L1/PD-L2 ligands and the attack reaction on tumor cells. The antitumor effect is achieved by releasing effector T-cells, reducing the function, number and suppressor activity of intratumoral Tregs. For antitumor drug therapy, anti-PD-1 and anti-PD-L1 monoclonal antibodies are used. This therapy is accompanied by various adverse events that are associated with the ability of PD-1 to interact with CD80 and the second PD-L2 ligand. Encouraging results of anti-PD-1/PD-L therapy in ovarian cancer resistant to platinum-containing chemotherapy may become an additional option in the treatment against the progression of ovarian cancer.

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About the authors

Varvara N. Zhurman

Primorsky Regional Oncological Dispensary

Author for correspondence.
ORCID iD: 0000-0002-6927-3336
SPIN-code: 1781-0007

M.D., Cand. Sci. (Med.), Oncologist

Russian Federation, Vladivostok, Russia


  1. Ngoi NY, Heong V, Ow S, Chay WY, Kim HS, Choi CH, Goss G, Goh JC, Tai BC, Lim DG, Kaliaperumal N, Au VB, Connolly JE, Kim JW, Friedlander M, Kim K, Tan DS. A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA). Int J Gynecol Cancer. 2020;30(8):1239–1242. doi: 10.1136/ijgc-2020-001604.
  2. Krishnan V, Berek JS, Dorigo O. Immunotherapy in ovarian cancer. Curr Probl Cancer. 2017;41(1):48–63. doi: 10.1016/j.currproblcancer.2016.11.003.
  3. Drakes ML, Mehrotra S, Aldulescu M, Potkul RK, Liu Y, Grisoli A, Joyce C, O'Brien TE, Stack MS, Stiff PJ. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand-1 (PD-L1) in ovarian cancer. J Ovarian Res. 2018;11(1):43. doi: 10.1186/s13048-018-0414-z.
  4. A study in ovarian cancer patients evaluating rucaparib and nivolumab as maintenance treatment following response to front-line platinum-based chemotherapy. (access date: 10.12.2022).
  5. Peyraud F, Italiano A. Combined PARP inhibition and immune checkpoint therapy in solid tumors. Cancers. 2020;12(6):1502. doi: 10.3390/cancers12061502.
  6. Klyuchagina UI, Sokolova ZA, Baryshnikova MA. Role of PD-1 receptor and its ligands PD-L1 and PD-L2 in cancer immunotherapy. Onkopediatriya. 2017;4(1):49–55. (In Russ.)
  7. Padmanabhan S, Zou Y, Vancurova I. Immunoblotting analysis of intracellular PD-L1 levels in interferon-γ-treated ovarian cancer cells stably transfected with Bcl3 shRNA. Methods Mol Biol. 2020;2108:211–220. doi: 10.1007/978-1-0716-0247-8_18.
  8. Stanczak MA, Siddiqui SS, Trefny MP, Thommen DS, Boligan KF, von Gunten S, Tzankov A, Tietze L, Lardinois D, Heinzelmann-Schwarz V, von Bergwelt-Baildon M, Zhang W, Lenz HJ, Han Y, Amos CI, Syedbasha M, Egli A, Stenner F, Speiser DE, Varki A, Zippelius A, Läubli H. Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells. J Clin Invest. 2018;128(11):4912–4923. doi: 10.1172/JCI120612.
  9. Lin H, Wei S, Hurt EM, Green MD, Zhao L, Vatan L, Szeliga W, Herbst R, Harms PW, Fecher LA, Vats P, Chinnaiyan AM, Lao CD, Lawrence TS, Wicha M, Hamanishi J, Mandai M, Kryczek I, Zou W. Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. J Clin Invest. 2018;128(2):805–815. doi: 10.1172/JCI96113.
  10. Yang K, Zhao W, Lou G, Rong Z, Xu H, Wang W, Song W, Cai Y, Hou Y, Li K. An immunophenotyping of ovarian cancer with clinical and immunological significance. Front Immunol. 2018;9:757. doi: 10.3389/fimmu.2018.00757.
  11. Fessas P, Lee H, Ikemizu S, Janowitz T. A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017;44(2):136–140. doi: 10.1053/j.seminoncol.2017.06.002.
  12. Friese C, Harbst K, Borch TH, Westergaard MCW, Pedersen M, Kverneland A, Jönsson G, Donia M, Svane IM, Met Ö. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer. Sci Rep. 2020;10(1):3914. doi: 10.1038/s41598-020-60738-4.
  13. Abdel-Wahab N, Alshawa A, Suarez-Almazor ME. Adverse events in cancer immunotherapy. Adv Exp Med Biol. 2017;995:155–174. doi: 10.1007/978-3-319-53156-4_8.
  14. Chatterjee J, Dai W, Aziz NHA, Teo PY, Wahba J, Phelps DL, Maine CJ, Whilding LM, Dina R, Trevisan G, Flower KJ, George AJT, Ghaem-Maghami S. Clinical use of programmed cell death-1 and its ligand expression as discriminatory and predictive markers in ovarian cancer. Clin Cancer Res. 2017;23(13):3453–3460. doi: 10.1158/1078-0432.CCR-16-2366.
  15. Wang Q, Lou W, Di W, Wu X. Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer. Int Immunopharmacol. 2017;52:7–14. doi: 10.1016/j.intimp.2017.08.017.
  16. Zhu J, Wen H, Ju X, Bi R, Zuo W, Wu X. Clinical significance of programmed death ligand-1 and intra-tumoral CD8+ T lymphocytes in ovarian carcinosarcoma. PLoS One. 2017;12(1):e0170879. doi: 10.1371/journal.pone.0170879.
  17. Drakes ML, Czerlanis CM, Stiff PJ. Immune checkpoint blockade in gynecologic cancers: State of affairs. Cancers. 2020;12(11):3301. doi: 10.3390/cancers12113301.
  18. Zhu X, Lang J. Soluble PD-1 and PD-L1: Predictive and prognostic significance in cancer. Oncotarget. 2017;8(57):97671–97682. doi: 10.18632/oncotarget.18311.
  19. Disis ML, Patel MR, Pant S, Infante JR, Lockhart AC, Kelly K, Beck JT, Gordon MS, Weiss GJ, Ejadi S, Taylor MH, von Heydebreck A, Chin KM, Cuillerot J-M, Gulley JL. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial. J Clin Oncol. 2015;33(15):5509. doi: 10.1200/jco.2015.33.15_suppl.5509.
  20. Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36(17):1714–1768. doi: 10.1200/JCO.2017.77.6385.
  21. Phase II study of Ipilimumab monotherapy in recurrent platinum-sensitive ovarian cancer — study results. (access date: 10.12.2022).
  22. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455-65. doi: 10.1056/NEJMoa1200694.
  23. Konstantinopoulos PA, Waggoner SE, Vidal GA, Mita MM, Fleming GF, Holloway RW, Le LV, Sachdev JC, Chapman-Davis E, Colón-Otero G, Penson RT, Matulonis UA, Kim YB, Moore KN, Swisher EM, Dezube BJ, Wang J, Buerstatte N, Arora S, Munster PN. TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of Niraparib + Pembrolizumab in patients (pts) with advanced -triple-negative breast cancer or recurrent ovarian cancer (ROC) — Results from ROC cohort. J Clin Oncol. 2018;36:106–106. doi: 10.1200/JCO.2018.36.15_suppl.106.
  24. A phase II study of Nivolumab/Bevacizumab. (access date: 10.12.2022)
  25. ATALANTE: Atezolizumab vs placebo phase III study in late relapse ovarian cancer treated with chemotherapy + Bevacizumab. (access date: 10.12.2022).
  26. Niraparib in combination with pembrolizumab in patients with triple-negative breast cancer or ovarian cancer. (access date: 10.12.2022).
  27. PEMBRO with chemo in neo adj treatment of ovarian cancer. Available from: (access date: 10.12.2022).
  28. Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology. 2017;6(2):e1277308. doi: 10.1080/2162402X.2016.1277308.
  29. Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner ES, Schwartz PE, Santin AD. Exceptional response to Pembrolizumab in a metastatic, chemotherapy/radiation-resistant ovarian cancer patient harboring a PD-L1-genetic rearrangement. Clin Cancer Res. 2018;24(14):3282–3291. doi: 10.1158/1078-0432.CCR-17-1805.
  30. A study in ovarian cancer patients evaluating rucaparib and nivolumab as maintenance treatment following response to front-line platinum-based chemotherapy. (access date: 10.12.2022).
  31. Maleki Vareki S, Garrigós C, Duran I. Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol. 2017;116:116–124. doi: 10.1016/j.critrevonc.2017.06.001.
  32. Olaparib, durvalumab, and tremelimumab in treating patients with recurrent or refractory ovarian, fallopian tube or primary peritoneal cancer with BRCA1 or BRCA2 mutation. (access date: 10.12.2022).
  33. Pembrolizumab in treating participants with metastatic, recurrent or locally advanced cancer and genomic instability. (access date: 10.12.2022).
  34. Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016;7(12):13587–13598. doi: 10.18632/oncotarget.7277.
  35. Kotsyrbiy EA, Tychonov YN, Nazarova IV, Reznichek IO, Tumanina AN, Gorelik MZ. Practical application of the cell block technique for the diagnostics of the tumors of the pancreas and of other localizations. Pacific Medical Journal. 2020;(4):90–92. (In Russ.) doi: 10.34215/1609-1175-2020-4-90-92.

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