{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:28:33Z","timestamp":1787646513840,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2025GGA015"],"award-info":[{"award-number":["2025GGA015"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Resistance to immune checkpoint blockade in gastric cancer often arises from defective antigen presentation due to MHC\u2010I downregulation, yet strategies to restore MHC\u2010I expression remain limited. Here, using the natural alkaloid koumine as a chemical probe, we identified IGF2BP3 as a druggable regulator of MHC\u2010I antigen presentation. Network pharmacology, proteomics, surface plasmon resonance, and cellular thermal shift assays were used to identify and validate koumine's target. Genetic rescue experiments, loss\u2010of\u2010function studies, in\u00a0vitro T\u2010cell co\u2010culture assays, and in\u00a0vivo gastric cancer mouse models were performed to confirm the causal relationship. m6A\u2010seq and ChIP\u2010seq analyses delineated the downstream epigenetic pathway. Koumine binds IGF2BP3 and promotes its proteasome\u2010dependent degradation, which reduces m6A enrichment on EED mRNA, accelerates EED decay, lowers H3K27me3, and derepresses IRF transcription, thereby restoring MHC\u2010I expression and enhancing CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell killing. Crucially, koumine enhanced the efficacy of anti\u2010PD\u20101 therapy in gastric cancer mouse models, suppressing tumor growth and fostering an immunologically active tumor microenvironment characterized by CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration and activation. This study identifies IGF2BP3 as an actionable target for improving antigen presentation and establishes koumine as a valuable chemical probe to dissect this pathway, with implications for immunotherapy sensitization beyond gastric cancer.\n                  <\/jats:p>","DOI":"10.1111\/cas.70514","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:57:11Z","timestamp":1787644631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of\n                    <scp>IGF2BP3<\/scp>\n                    \u2010Mediated Immune Response Activation in Enhancing Immunotherapy of Koumine for Gastric Cancer"],"prefix":"10.1111","author":[{"given":"Qiu","family":"Hongqiang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Fujian Medical University Union Hospital  Fuzhou China"},{"name":"School of Pharmacy Fujian Medical University  Fuzhou 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