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Here, using a genetically engineered mouse model with conditional YAP hyperactivation and Tp53 deletion in gastric Atp4b\n                    <jats:sup>+<\/jats:sup>\n                    cells (AYP), we show this \u201cdouble\u2010hit\u201d alone suffices to recapitulate human refractory GC, including histopathological heterogeneity, multi\u2010organ metastasis, and intrinsic PD\u20101 resistance. We identified BST2 as a direct YAP\u2010TEAD transcriptional target. In human GC, BST2\u2010high tumor correlates with poor anti\u2010PD\u20101 response. Mechanistically, tumor cell\u2010derived BST2 engages the inhibitory receptor PIRA2 on neutrophils and liver Kupffer cells, instructing an immunosuppressive, pro\u2010metastatic phenotype that inhibits T cells antitumor response and confers PD\u20101 resistance. Therapeutically, dual BST2\/PD\u20101 blockade in the AYP model suppresses primary tumor growth and eradicates established liver metastases. Thus, YAP activation, cooperating with TP53 loss, fuels metastatic GC and immunotherapy resistance via BST2 induction.\n                  <\/jats:p>","DOI":"10.1002\/advs.77708","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:05:18Z","timestamp":1789981518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the YAP\u2010BST2 Axis Overcomes Intrinsic Anti\u2010PD\u20101 Resistance in Metastatic Gastric Cancer"],"prefix":"10.1002","author":[{"given":"Weihong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Zhongshan Hospital Fudan University  Shanghai China"},{"name":"School of Medicine Shanghai Tenth People's Hospital Tongji University Cancer Center Tongji University  Shanghai 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