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While immune checkpoint blockade (ICB) targeting the programmed cell death protein 1 (PD\u20101)\/programmed death\u2010ligand 1 (PD\u2010L1) axis has revolutionized oncology, its success in ovarian cancer has been strikingly limited. This review synthesizes emerging evidence that extends the role of PD\u2010L1 beyond canonical immune evasion to include tumor\u2010cell\u2010intrinsic mechanisms that may contribute to chemoresistance. We explore the \u201cdual shield\u201d function of PD\u2010L1, detailing how its non\u2010canonical, intracellular signaling promotes tumor cell survival, stemness, and therapy resistance. Mechanistically, preclinical studies indicate that PD\u2010L1 can modulate DNA damage responses and may enhance anti\u2010apoptotic signaling, rewire cellular metabolism, and regulate autophagy. Nuclear PD\u2010L1 has also been linked to DNA repair machinery in preclinical cancer models, suggesting a potential mechanism of resistance to DNA\u2010damaging therapy; however, direct mechanistic evidence in ovarian cancer remains limited and is still emerging. The tumor microenvironment further amplifies this axis through cytokine networks and physical barriers. These tumor\u2010intrinsic survival mechanisms may help explain why PD\u20101\/PD\u2010L1 blockade alone has shown limited efficacy in ovarian cancer. Overcoming this requires rational combination strategies that simultaneously disrupt PD\u2010L1\u2010mediated immune suppression and its cell\u2010autonomous pro\u2010survival functions. Overall, this dual\u2010function framework positions PD\u2010L1 as a multifunctional therapeutic node and provides a rationale for combination strategies targeting both immune escape and tumor\u2010intrinsic resistance mechanisms.<\/jats:p>","DOI":"10.1002\/cam4.72296","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:29:29Z","timestamp":1789705769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    in Ovarian Cancer: Immune Evasion, Tumor\u2010Intrinsic Signaling, and Chemoresistance"],"prefix":"10.1002","volume":"15","author":[{"given":"Zhiyang","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Xijing Hospital Fourth Military Medical University  Xi'an 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