Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer

Abstract

Immunotherapies have revolutionized the treatment of a variety of cancers. Epithelial ovarian cancer is the most lethal gynecologic malignancy, and the rate of advanced tumor progression or recurrence is as high as 80%. Current salvage strategies for patients with recurrent ovarian cancer are rarely curative. Recurrent ovarian cancer is a “cold tumor”, predominantly due to a lack of tumor antigens and an immunosuppressive tumor microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade as a monotherapy, the response rate was only 8.0-22.2%. In this review, we illustrate the status of cold tumors in ovarian cancer and summarize the existing clinical trials investigating PD-1/PD-L1 blockade in recurrent ovarian cancer. Increasing numbers of immunotherapy combination trials have been set up to improve the response rate of EOC. The current preclinical and clinical development of immunotherapy combination therapy to convert an immune cold tumor into a hot tumor and their underlying mechanisms are also reviewed. The combination of anti-PD-1/PD-L1 with other immunomodulatory drugs or therapies, such as chemotherapy, antiangiogenic therapies, poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, and oncolytic therapy, could be beneficial. Further efforts are merited to transfer these results to a broader clinical application.

A multidimensional pan‐cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma

“…46 Meanwhile, our results show that DCAF13 was significantly negatively correlated with the immune score, MHC, and IPS, suggesting that high DCAF13 expression may lead to the immunosuppressive microenvironment and immunotherapy resistance. Due to the immune-suppressive tumor microenvironment, the therapeutic efficacy of anti-PD-(L)1 is far from expected in diverse cancers, such as glioblastoma, 47 ovarian cancer, 48,49 prostate cancer 50 and pancreatic cancer. 51,52 A recent report from «Cell» reveals that quiescent cancer cells form clusters with reduced immune infiltration by single-cell RNA sequencing.…”

TCR CDR3‐antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?

“…Ovarian cancer in general is often referred to as immunologically cold, and indeed a response to immune checkpoint blockade is rare, below 20%. [ 24,25 ] However, the response rate is not zero, raising the question of whether an identification of an ongoing response per the approaches applied here could identify cases that would be particularly responsive to immunotherapies.…”

Comparative glycoproteomics study on the surface of SKOV3 versus IOSE80 cell lines

“…Immunotherapy is a new strategy proposed in recent years to treat ovarian malignant tumors, aiming to enhance the ability of patients’ immune system to recognize and attack tumor cells ( Morand et al, 2021 ). Among them, the research on PD-L1 inhibitors in ovarian cancer, especially advanced ovarian cancer, recurrent ovarian cancer, and platinum-sensitive or platinum-resistant ovarian cancer, has been carried out successively ( Mittica et al, 2016 ; Pujade-Lauraine et al, 2018 ; Zhang et al, 2022 ). Our findings provide new evidence for the application of the PD-L1 inhibitor in the treatment of ovarian cancer.…”