Immunotherapy advancements in high-grade serous ovarian cancer: From promise to practice

High-grade serous ovarian carcinoma (HGSC) is the most common epithelial ovarian cancer subtype, with high recurrence rates and poor overall survival. Despite progress with cytoreductive surgery, platinum-based chemotherapy, and poly(ADP-ribose) polymerase (PARP) inhibitors, treatment outcomes remain poor, underscoring the need for novel approaches. Immunotherapy is currently the standard of care for the management of several solid tumors, but its role in HGSC is still emerging. This review synthesizes current evidence on the immune landscape of HGSC, predictive biomarkers, resistance mechanisms, and therapeutic strategies including immune checkpoint inhibitors, vaccines, adoptive cell therapies, oncolytic viruses, and antibody-drug conjugates (ADCs) which interact with the immune system. While checkpoint blockade has demonstrated modest efficacy in unselected populations, ADCs targeting folate receptor alpha (FRα) and trophoblast cell-surface antigen 2 (TROP2) have shown the most encouraging clinical results. Biomarkers such as homologous recombination deficiency, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutational burden, and neoantigen load may enable patient selection, although none are fully validated for immunotherapies. Combination regimens with PARP inhibitors, anti-angiogenic agents, or chemotherapy offer potential synergy, but optimal sequencing remains undefined. Toxicity management is essential, as immune-related adverse events, although generally manageable, may overlap with the side effects of other systemic therapies. Multidisciplinary approaches and patient education are key to safe integration. Overall, immunotherapy represents a promising avenue for selected patients with HGSC. ADCs are leading current clinical advances. Future priorities include biomarker-driven trial designs, strategic treatment sequencing, and innovative combination strategies to maximize therapeutic benefit while minimizing toxicity. • Biomarker-guided selection is key to effective immunotherapy in HGSC • Maintenance strategies must prioritize low toxicity and quality of life preservation • Early-line trials integrating biomarkers could transform HGSC outcomes • Future trials should focus on optimal treatment sequencing