{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:12:32Z","timestamp":1791573152042,"version":"4.3.4"},"reference-count":179,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["ZYJC21043"],"award-info":[{"award-number":["ZYJC21043"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2023YFS0111"],"award-info":[{"award-number":["2023YFS0111"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunotherapy combined with chemotherapy has become the standard treatment for HER2\u2010negative gastric cancer (GC), but its clinical benefits remain limited, with a median progression\u2010free survival (mPFS) of 6\u20138\u2009months and median overall survival (mOS) of 15\u201318\u2009months. These outcomes are particularly poor in patients with CPS\u2009&lt;\u20091. The marked heterogeneity of GC, along with primary and secondary resistance, presents significant clinical challenges and underscores the urgent need for novel therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Advances<\/jats:title>\n                    <jats:p>To address these limitations, several combination therapies are being explored. Anti\u2010VEGF therapy combined with immune checkpoint inhibitors (ICIs) has shown synergistic effects by enhancing immune cell infiltration and reducing tumor\u2010mediated immunosuppression, thereby improving response rates and survival. Radiotherapy combined with ICIs also holds promise, with low\u2010dose radiation remodeling the tumor microenvironment and high\u2010dose radiation inducing immunogenic cell death. Other potential combinations include PD\u20101\/PD\u2010L1 inhibitors paired with targeted therapies against HER2, FGFR2, DKK1, PARP, LSD1, HDAC, and other emerging targets. Novel approaches such as hyperbaric oxygen therapy, oncolytic viruses, metabolic modulators, and fecal microbiota transplantation are also under investigation to further enhance immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These multimodal strategies represent a promising shift toward personalized, mechanism\u2010driven immunotherapy sensitization. By targeting diverse pathways to overcome immune resistance, they aim to reshape the tumor microenvironment, restore immune responsiveness, and improve outcomes in GC. While many remain in early\u2010stage development, accumulating evidence supports their potential. Future research should prioritize optimizing combination regimens, clarifying resistance mechanisms, and identifying predictive biomarkers through multi\u2010omics and artificial intelligence to enable more precise, individualized immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71065","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:44:57Z","timestamp":1753091097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Current Advances and Future Directions for Sensitizing Gastric Cancer to Immune Checkpoint Inhibitors"],"prefix":"10.1002","volume":"14","author":[{"given":"Wenke","family":"Li","sequence":"first","affiliation":[{"name":"Gastric Cancer Center\/Cancer Center, West China Hospital, Sichuan University  Chengdu Sichuan 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