Immunotherapy in Gynecologic Cancers: Current Evidence, Biomarker-Driven Practice, and Future Directions

Immune checkpoint blockade has become an important component of treatment for several gynecologic malignancies, but its clinical value varies substantially by tumor lineage, molecular subtype, disease setting, and treatment backbone. This narrative review summarizes the biological rationale, clinical evidence, predictive biomarkers, combination strategies, toxicity considerations, and future directions of immunotherapy across gynecologic cancers. In cervical cancer, checkpoint blockade has evolved from later-line recurrent disease to first-line systemic therapy and, more recently, to curative-intent chemoradiotherapy combinations. In endometrial cancer, mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) tumors show the clearest sensitivity to programmed cell death protein 1 (PD-1) blockade, whereas mismatch repair-proficient/microsatellite stable (pMMR/MSS) disease generally requires combination strategies. In ovarian cancer, broad unselected checkpoint inhibitor strategies have generally failed; ENGOT-ov65/KEYNOTE-B96 demonstrated statistically significant progression-free survival (PFS) and overall survival (OS) improvement with pembrolizumab plus weekly paclitaxel, with or without bevacizumab, in a defined platinum-resistant population, although the absolute median PFS gain in PD-L1 combined positive score (CPS) ≥1 disease was modest. Gestational trophoblastic neoplasia (GTN) offers a biologically distinctive setting because of trophoblastic immune tolerance, whereas selected rare gynecologic malignancies may be considered for immunotherapy on the basis of HPV association, tumor-agnostic biomarkers, or signals observed in clear-cell cohorts. Accordingly, the clinical value of immunotherapy should be interpreted according to tumor lineage, disease setting, validated biomarkers, treatment backbone, and the incremental contribution of each treatment component.