Anti-PD-L1/PD-1 Immune Therapies in Ovarian Cancer: Basic Mechanism and Future Clinical Application

Overview

Journal Int J Clin Oncol

Specialty Oncology

Date 2016 Mar 13

PMID 26968587

Citations 20

Authors

Masaki Mandai

Junzo Hamanishi

Kaoru Abiko

Noriomi Matsumura

Tsukasa Baba

Ikuo Konishi

Affiliations

Soon will be listed here.

Abstract

Tumor immune therapy, especially anti-programmed cell death ligand-1/programmed cell death-1 (PD-L1/PD-1) treatment, is currently the focus of substantial attention. Ovarian cancer is the leading cause of mortality from gynecological malignancies, and novel treatment modalities, including immune therapy, are needed. However, a basic understanding of tumor immunity associated with the PD-L1/PD-1 signal has only recently emerged. In this review, we first discuss the importance of local tumor immunity, which affects the clinical outcome of ovarian cancer. We subsequently provide an overview of the basic findings regarding how the PD-L1/PD-1 signal influences local tumor immunity in ovarian cancer. Finally, we discuss what is needed to apply immune therapy in future clinical medicine.

Citing Articles

Dysgerminomas: germ cell tumors exhibit high expression of PD-L1 and associated with high TILs and good prognosis.

Alwosaibai K, Alruwaii Z, Mashhour M, Almsned F, Asraf R, Alrsheedy W Sci Rep. 2024; 14(1):24191.

PMID: 39406772 PMC: 11480429. DOI: 10.1038/s41598-024-74192-z.

IFNγ-Induced Bcl3, PD-L1 and IL-8 Signaling in Ovarian Cancer: Mechanisms and Clinical Significance.

Reddy S, Sadia F, Vancura A, Vancurova I Cancers (Basel). 2024; 16(15).

PMID: 39123403 PMC: 11311860. DOI: 10.3390/cancers16152676.

Immunohistochemical Profiling of PD-1, PD-L1, CD8, MSI, and p53 and Prognostic Implications in Advanced Serous Ovarian Carcinoma: A Retrospective Study.

Dergham A, De Paula C, Nagashima S, Olandoski M, de Noronha L, Sotomaior V J Pers Med. 2023; 13(7).

PMID: 37511658 PMC: 10381449. DOI: 10.3390/jpm13071045.

Dynamic host immunity and PD-L1/PD-1 blockade efficacy: developments after "IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer".

Abiko K, Hamanishi J, Matsumura N, Mandai M Br J Cancer. 2022; 128(3):461-467.

PMID: 36068276 PMC: 9938281. DOI: 10.1038/s41416-022-01960-x.

MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells.

Moghbeli M J Ovarian Res. 2021; 14(1):127.

PMID: 34593006 PMC: 8485521. DOI: 10.1186/s13048-021-00882-1.

References

Zhang L, Conejo-Garcia J, Katsaros D, Gimotty P, Massobrio M, Regnani G . Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177. View

Kooi S, Zhang H, Patenia R, Edwards C, Platsoucas C, Freedman R . HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol. 1996; 174(2):116-28. DOI: 10.1006/cimm.1996.0301. View

Vermeij R, de Bock G, Leffers N, ten Hoor K, Schulze U, Hollema H . Tumor-infiltrating cytotoxic T lymphocytes as independent prognostic factor in epithelial ovarian cancer with wilms tumor protein 1 overexpression. J Immunother. 2011; 34(6):516-23. DOI: 10.1097/CJI.0b013e31821e012f. View

Guo Z, Wang X, Cheng D, Xia Z, Luan M, Zhang S . PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer. PLoS One. 2014; 9(2):e89350. PMC: 3937343. DOI: 10.1371/journal.pone.0089350. View

Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T . Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. J Clin Oncol. 2015; 33(34):4015-22. DOI: 10.1200/JCO.2015.62.3397. View

Topalian S, Hodi F, Brahmer J, Gettinger S, Smith D, Mcdermott D . Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26):2443-54. PMC: 3544539. DOI: 10.1056/NEJMoa1200690. View

Wei H, Zhao L, Li W, Fan K, Qian W, Hou S . Combinatorial PD-1 blockade and CD137 activation has therapeutic efficacy in murine cancer models and synergizes with cisplatin. PLoS One. 2013; 8(12):e84927. PMC: 3868659. DOI: 10.1371/journal.pone.0084927. View

Bachmayr-Heyda A, Aust S, Heinze G, Polterauer S, Grimm C, Braicu E . Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients--a study of the OVCAD consortium. BMC Cancer. 2013; 13:422. PMC: 3848589. DOI: 10.1186/1471-2407-13-422. View

Zou W, Chen L . Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008; 8(6):467-77. DOI: 10.1038/nri2326. View

10.

Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T . Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. Cancer Res. 2015; 75(23):5034-45. DOI: 10.1158/0008-5472.CAN-14-3098. View

11.

Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G . Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15(8):852-61. DOI: 10.1016/S1470-2045(14)70228-1. View

12.

Guo Z, Wang H, Meng F, Li J, Zhang S . Combined Trabectedin and anti-PD1 antibody produces a synergistic antitumor effect in a murine model of ovarian cancer. J Transl Med. 2015; 13:247. PMC: 4517526. DOI: 10.1186/s12967-015-0613-y. View

13.

Duraiswamy J, Kaluza K, Freeman G, Coukos G . Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 2013; 73(12):3591-603. PMC: 3686913. DOI: 10.1158/0008-5472.CAN-12-4100. View

14.

Hamid O, Robert C, Daud A, Hodi F, Hwu W, Kefford R . Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013; 369(2):134-44. PMC: 4126516. DOI: 10.1056/NEJMoa1305133. View

15.

Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K . IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015; 112(9):1501-9. PMC: 4453666. DOI: 10.1038/bjc.2015.101. View

16.

Burger R, Brady M, Bookman M, Fleming G, Monk B, Huang H . Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011; 365(26):2473-83. DOI: 10.1056/NEJMoa1104390. View

17.

Poveda A, Selle F, Hilpert F, Reuss A, Savarese A, Vergote I . Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial. J Clin Oncol. 2015; 33(32):3836-8. DOI: 10.1200/JCO.2015.63.1408. View

18.

Peng W, Liu C, Xu C, Lou Y, Chen J, Yang Y . PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines. Cancer Res. 2012; 72(20):5209-18. PMC: 3476734. DOI: 10.1158/0008-5472.CAN-12-1187. View

19.

Abiko K, Mandai M, Hamanishi J, Yoshioka Y, Matsumura N, Baba T . PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. Clin Cancer Res. 2013; 19(6):1363-74. DOI: 10.1158/1078-0432.CCR-12-2199. View

20.

Webb J, Milne K, Watson P, deLeeuw R, Nelson B . Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res. 2013; 20(2):434-44. DOI: 10.1158/1078-0432.CCR-13-1877. View