{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:00:25Z","timestamp":1790125225253,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC0541"],"award-info":[{"award-number":["2025ZNSFSC0541"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017661","name":"China Health Promotion Foundation","doi-asserted-by":"publisher","award":["23H1547"],"award-info":[{"award-number":["23H1547"]}],"id":[{"id":"10.13039\/501100017661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Immunosuppression in ovarian cancer is primarily driven by myeloid\u2010derived suppressor cells (MDSCs). This study identifies karyopherin \u03b12 (KPNA2) as a novel regulator of this immunosuppressive process through the NF\u2010\u03baB\/CCL2\/CCR2 axis. Elevated KPNA2 expression correlates with increased intratumoral MDSC accumulation and impaired CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell function. Mechanistically, KPNA2 directly binds to and facilitates nuclear translocation of NF\u2010\u03baB\/p65, thereby driving CCL2 transcription, while also exhibiting an auxiliary, p65\u2010independent function in CCL2 induction. Secreted CCL2 recruits MDSCs in a CCR2\u2010dependent manner, establishing a potent immunosuppressive tumor microenvironment. Therapeutic targeting via MDSC depletion, pharmacological CCR2 blockade, or direct KPNA2 knockdown effectively inhibited metastasis, enhanced CD8+ T\u2010cell infiltration, and suppressed tumor growth. Importantly, CCR2 inhibition synergized with anti\u2010PD\u2010L1 therapy, revealing a promising combination immunotherapeutic strategy for KPNA2\u2010high ovarian cancer. These findings establish the KPNA2\u2010governed NF\u2010\u03baB\/CCL2\/CCR2 pathway as a central mechanism of immune evasion and a viable target for combination immunotherapy in ovarian cancer.\n                  <\/jats:p>","DOI":"10.1111\/cas.70440","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T02:24:16Z","timestamp":1782181456000},"page":"2461-2479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>KPNA2<\/scp>\n                    Drives Immunosuppression in Ovarian Cancer via\n                    <scp>CCL2<\/scp>\n                    \/\n                    <scp>CCR2<\/scp>\n                    \u2010Dependent\n                    <scp>MDSC<\/scp>\n                    Recruitment"],"prefix":"10.1111","volume":"117","author":[{"given":"Qingli","family":"Li","sequence":"first","affiliation":[{"name":"Cancer Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education West China Second University Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education West China Second University Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education West China Second University Hospital, Sichuan University  Chengdu Sichuan 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