Abstract
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by leveraging the immune system's capacity to fight gynecologic cancer. This review summarizes the current status and future perspectives of ICIs in the treatment of cervical, endometrial, and ovarian cancers and rare tumors. ICIs have demonstrated significant efficacy in tumors with high tumor mutational burden and immune markers such as PD-L1 expression and microsatellite instability. In cervical cancer, the integration of ICIs has shown promise at various stages of treatment, including advanced and recurrent settings. In endometrial cancer, molecular classification has facilitated targeted immunotherapy strategies, with notable success in mismatch repair-deficient (dMMR) tumors. However, challenges remain in the treatment of microsatellite stable endometrial and epithelial ovarian cancers due to their relatively low immunogenicity. Combination therapies, including ICIs with angiogenesis inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, or chemotherapy, are being actively investigated to improve response rates. Several phase II and case series showed promising response to ICIs in vulvar/vaginal cancer and gestational trophoblastic neoplasia, though the efficacy in genital tract melanoma is still unclear. Despite these advances, the management of immune-related adverse events and the identification of reliable biomarkers for patient selection remain critical. ICIs are poised to redefine the therapeutic landscape of gynecologic oncology, offering hope for improved outcomes and personalized treatment strategies.