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However, the proportion of patients who can benefit from it and its overall efficacy remain limited. Here the aim is to identify key dual\u2010function targets that both inhibit proliferation and suppress immune evasion. Using whole genome\u2010wide CRISPR\u2010Cas9\u2010based screening, the serine\/threonine kinase T\u2010lymphokine\u2010activated killer cell\u2010originated protein kinase (TOPK) is identified as a key regulator of PD\u2010L1 in gastric cancer upon IFN\u2010\u03b3 stimulation. Mechanical study is performed to explore the role of TOPK in promoting GC malignancy and immune evasion in vitro and vivo. Higher TOPK levels in tumor tissues are observed, correlated with clinical stages, efficacy and survival. Upon IFN\u2010\u03b3 stimulation, TOPK phosphorylates eIF4F complex component eIF4A1 to increase its unwinding activity of STAT1 mRNA, enhancing STAT1 translation efficiency. This process leads to adaptive overexpression of PD\u2010L1 and IDO1, resulting in immunometabolic suppression through PD\u2010L1\u2010mediated inhibition, IDO1\u2010induced tryptophan depletion and kynurenine production. TOPK inhibitors reshape tumor immunometabolic microenvironment to trigger anti\u2010tumor immunity in GC. The IFN\u2010\u03b3\u2010TOPK\u2010eIF4F\u2010STAT1\u2010PD\u2010L1\/IDO1 axis as a crucial regulator of the tumor immunometabolic microenvironment and provide novel insights into the combination of targeted therapy and immunotherapy for GC treatment.<\/jats:p>","DOI":"10.1002\/advs.202517380","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T17:14:23Z","timestamp":1766164463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TOPK Inhibition Promotes Anti\u2010Tumor Immunity Via eIF4F Complex Mediated STAT1 Translation in Gastric Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-1332","authenticated-orcid":false,"given":"Junbing","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Division of Gastrointestinal Cancer Translational Research 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