Advances in the application of immune checkpoint inhibitors in gynecological tumors.

Abstract

Immune checkpoints are regulatory molecules that suppress immune effector cells, and are essential for maintaining tolerance, preventing autoimmune reactions, and minimizing tissue damage by controlling the duration and intensity of the immune responses. However, immune checkpoints are frequently upregulated during cancer and dampen the anti-tumor immune responses. Immune checkpoint inhibitors (ICIs) have been effective against multiple tumors, and have improved patients' survival outcomes. Recent clinical trials have also reported promising therapeutic effects of ICIs in some gynecological cancers. To review the current research and future directions in the treatment of gynecological malignancies, including ovarian, cervical and endometrial cancers, using ICIs. Currently, cervical and ovarian cancers are the only gynecological tumors that are treated by immunotherapeutic approaches. In addition, ICIs, chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells targeting endometrial tumors, especially those originating in the vulva and fallopian tubes, are under development. Nevertheless, the molecular mechanism underlying the effects of ICIs, especially in combination with chemotherapy, radiation therapy, anti-angiogenesis drugs and poly ADP ribose polymerase inhibitors (PARPi), needs to be elucidated. Furthermore, novel predictive biomarkers have to be identified in order to increase the therapeutic efficacy of ICIs while reducing adverse reactions.