{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:14:46Z","timestamp":1784556886781,"version":"3.55.0"},"reference-count":179,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitors and antibody\u2013drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, and emerging directions for immune checkpoint blockade and antibody\u2013drug conjugates in endometrial, cervical, and ovarian cancers. In endometrial cancer, molecular classification and mismatch repair status have transformed treatment selection, with PD-1 or PD-L1 blockade now integrated into first-line chemoimmunotherapy and recurrent disease management. HER2-directed and TROP-2-directed antibody\u2013drug conjugates are also emerging as biomarker-directed strategies. In cervical cancer, human papillomavirus-driven tumor biology, PD-L1 expression, and tissue factor expression support the use of checkpoint inhibitors, antibody\u2013drug conjugates, and therapeutic vaccine approaches across locally advanced and recurrent or metastatic settings. In ovarian cancer, single-agent checkpoint blockade has shown limited activity in unselected populations, but recent advances include biomarker-selected chemoimmunotherapy in platinum-resistant disease and clinically meaningful activity of folate receptor alpha-directed and HER2-directed antibody\u2013drug conjugates. Across gynecologic cancers, key challenges include refining predictive biomarkers, optimizing sequencing after prior immunotherapy exposure, managing overlapping toxicities, and designing trials that enrich for biologically responsive subgroups. Future progress will depend on integrating molecular classification, immune contexture, ADC target expression, and patient-specific clinical factors into treatment selection.<\/jats:p>","DOI":"10.3390\/cancers18142342","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"2342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunotherapy and Relevant Antibody\u2013Drug Conjugates in Gynecologic Oncology: Recent Advances, Ongoing Challenges, and Future Directions"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-9917","authenticated-orcid":false,"given":"Ting-Tai","family":"Yen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina Yi-Jin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene P.","family":"Toy","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"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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