{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:50:06Z","timestamp":1787755806097,"version":"build-2784847793"},"reference-count":77,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epithelial ovarian cancer (EOC) remains one of the most lethal gynecologic malignancies, largely owing to advanced-stage presentation, high rates of relapse, and the eventual emergence of therapeutic resistance. Despite the transformative success of immune checkpoint inhibitors (ICIs) across multiple solid tumors, their clinical impact in ovarian cancer has been comparatively modest. This literature review provides a comprehensive synthesis of recent advances in ICI strategies for ovarian cancer (OC), with particular emphasis on phase II and III clinical trials evaluating programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte\u2013associated protein 4 (CTLA-4), and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3)-directed therapies. Accumulating evidence indicates that PD-1\/PD-L1 monotherapy yields limited clinical activity in unselected OC populations, with low objective response rates and minimal survival benefit. Dual checkpoint blockade with PD-1 and CTLA-4 inhibitors demonstrates enhanced antitumor activity, particularly in clear cell ovarian carcinoma (CCOC), albeit at the expense of increased immune-related toxicity. Large randomized trials incorporating ICI into first-line chemotherapy or maintenance settings have largely failed to improve outcomes in biomarker-unselected cohorts. Available evidence demonstrates that combinatorial approaches integrating ICI with anti-angiogenic agents, PARP inhibitors, or neoadjuvant chemotherapy provide modest benefit in selected molecular and histologic subgroups. Early-phase investigations of TIM-3\u2013targeting strategies further expand the immunotherapeutic landscape, although clinical efficacy remains preliminary. Current evidence underscores that OC is not uniformly responsive to immunotherapy and that rational combination strategies, biomarker-driven patient selection, and improved understanding of tumor immune microenvironment heterogeneity are essential to unlocking the full therapeutic potential of ICI in this disease.<\/jats:p>","DOI":"10.3390\/ijms27114923","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Limited Clinical Benefit of Immune Checkpoint Inhibition in Ovarian Cancer with Opportunities in Selected Subtypes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0316-4907","authenticated-orcid":false,"given":"Zuzanna","family":"Ratka","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-6591","authenticated-orcid":false,"given":"Andrzej","family":"Gamian","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolfa Weigla Str., 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7978-6330","authenticated-orcid":false,"given":"Marta","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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