Focus on PD-1/PD-L1 as a Therapeutic Target in Ovarian Cancer

Abstract

Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. However, the data presented in the literature until now are not sufficient to allow for the identification and selection of patients who really respond to immunotherapy among those with ovarian cancer. Although there are some studies with favorable results, more prospective trials are needed in this sense. This review focuses on the current and future perspectives of PD-1/L1 blockade in ovarian cancer and analyzes the most important immune checkpoint inhibitors used, with the aim of achieving optimal clinical outcomes. Future studies and trials are needed to maximize the efficacy of immune checkpoint blockade therapy in ovarian cancer, as well as in all cancers, in general.

Keywords: PD-1/PD-L1; gynecological malignancy; lncRNAs; miRNAs; ovarian cancer.

Figure 1

Histogram for 5-year survival rate in gynaecological cancers, regardless of the stage of the disease at the moment of presentation [3,4].

Figure 2

The interaction between PD-1 and PD-L1 leads to dysfunction of tumor infiltrating lymphocytes and evasion of tumor cells from the immune system. (TCR—T cel receptor, MHC-major histocompatibility complex). Created with BioRender.com (Last accessed on 26 September 2022).

Figure 3

Antibody blockade of PD-1 and PD-L1. Anti-PD-1 and PD-L1 antibodies block the PD-1/PD-L1 signalling and enhance antitumor immune activity. Created with BioRender.com (Last accessed on 26 September 2022).