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The SWI\/SNF chromatin remodeling complex acts as a regulatory component of transcription, and our previous study found an immune\u2010active microenvironment and better response to immunotherapy of gastric cancer with\n                    <jats:italic>ARID1A<\/jats:italic>\n                    loss. However, little is known about the clinical significance of\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    , which encodes for another subunit of the SWI\/SNF complex, in gastric cancer (GC) patients. This study analyzed the association of SMARCA4 status with clinicopathological features, survival outcomes, therapeutic response, and immune microenvironment characteristics in three independent cohorts: Zhongshan Hospital (ZSHS) cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009442), Zhongshan Hospital immune checkpoint blockade (ZSHS\u2010ICB) cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941), and Samsung Medical Center cohort (SMC,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200951). SMARCA4\u2010deficient GC patients exhibit clinicopathological features associated with enhanced tumor aggressiveness, including a higher prevalence of poorly differentiated disease (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.034), pN3 stage at diagnosis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.059), E\u2010cadherin negative expression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and genomically stable (GS) and microsatellite stable\/epithelial\u2013mesenchymal transition molecular subtype (MSS\/EMT) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, respectively). Kaplan\u2013Meier analysis revealed that SMARCA4 deficiency indicated poor prognosis in GC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Moreover, SMARCA4 deficiency identified a subgroup of GC patients who exhibited poor outcomes despite receiving adjuvant chemotherapy in the GS subtype (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.029). In contrast, these patients demonstrated increased sensitivity to anti\u2010PD\u20101 therapy in both the ZSHS\u2010ICB (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.039) and SMC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.062) cohorts. Immunological analysis revealed a distinct immune profile characterized by abundant but exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in SMARCA4\u2010deficient GC. In conclusion, patients with SMARCA4\u2010deficient GC patients demonstrated poor prognosis but improved response to immunotherapy. These observed clinical outcomes may be attributed to the immunosuppressive microenvironment, highlighting the potential for developing novel therapeutic approaches. \u00a9 2025 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6495","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:41:08Z","timestamp":1762875668000},"page":"113-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical outcomes and immune contexture in\n                    <scp>SMARCA4<\/scp>\n                    \u2010deficient gastric cancer patients"],"prefix":"10.1002","volume":"268","author":[{"given":"Mengyao","family":"Sun","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University  Shanghai PR 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