{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:18Z","timestamp":1790931198708,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073299"],"award-info":[{"award-number":["82073299"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009991","name":"Department of Finance of Jilin Province","doi-asserted-by":"publisher","award":["2025SCZ34"],"award-info":[{"award-number":["2025SCZ34"]}],"id":[{"id":"10.13039\/501100009991","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Gastric cancer (GC) progression is driven by an immunosuppressive tumor microenvironment (TME). Kynureninase (KYNU) is upregulated in GC and linked to poor prognosis, while platelet factor 4 (PF4)\u2010induced nonclassical macrophages promote immune evasion. This study investigates whether KYNU regulates macrophage polarization via PF4 in GC. KYNU expression was modulated in GC cells to assess PF4 regulation and nonclassical macrophage polarization. Functional consequences were evaluated by proliferation, migration, invasion, and phagocytosis assays. Mechanistic studies included transcriptomics, PI3K\/Akt manipulation, and rescue experiments. In\u00a0vivo validation used a syngeneic mouse model, and clinical relevance was confirmed by multimarker tissue analysis. High KYNU expression in GC cells specifically promoted macrophage polarization toward a nonclassical phenotype characterized by S100A8 and MMP7 expression. These non\u2010classical polarized macrophages subsequently enhanced GC cell proliferation, migration, and invasion while suppressing phagocytic activity. Mechanistically, KYNU upregulated PF4 expression with the involvement of the PI3K\/Akt signaling pathway, which in turn drove nonclassical macrophage polarization. In\u00a0vivo studies demonstrated that KYNU promoted tumor growth through this pathway, whereas PI3K\/Akt inhibition suppressed both tumor progression and nonclassical macrophage infiltration. Clinical analysis further confirmed the coordinated upregulation of KYNU, p\u2010Akt, PF4, and S100A8 in human GC tissues. KYNU acts as a signaling transducer in GC, involving PI3K\/Akt to upregulate PF4, driving nonclassical macrophage polarization and tumor progression. This mechanism represents a novel pathogenic driver and a promising therapeutic target for reprogramming the immunosuppressive TME.<\/jats:p>","DOI":"10.1111\/cas.70458","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:43:27Z","timestamp":1782809007000},"page":"2676-2692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>KYNU<\/scp>\n                    in Gastric Cancer Cells Promotes Tumor Progression by Influencing Macrophage Polarization Via\n                    <scp>PF4<\/scp>"],"prefix":"10.1111","volume":"117","author":[{"given":"Xilun","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Endoscopy Center China\u2010Japan Union Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4497-0792","authenticated-orcid":false,"given":"Changfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Center China\u2010Japan Union Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanda","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Center China\u2010Japan Union Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Center China\u2010Japan Union Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Immunology, College of Basic Medical Sciences Jilin 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