{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:59:56Z","timestamp":1785560396911,"version":"3.56.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":193,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The combination of trastuzumab and chemotherapy, with or without pembrolizumab, is the current first-line standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer and gastroesophageal junction cancer. However, upon disease progression, subsequent therapies often yield limited clinical benefit. The mechanisms of drug resistance to trastuzumab remain unresolved. Current studies on its resistance mechanisms have largely focused on alterations in the HER2 pathway, including HER2 heterogeneity, reduced or absent HER2 expression, variations in HER2 dimerization, and mutations in downstream components, among others. Crucially, as a monoclonal antibody, the antitumor activity of trastuzumab is partially mediated by the immune system, yet the immunology-related mechanisms of resistance are frequently overlooked. In this review, we systematically analyse the outcomes of both successful and failed clinical trials of anti-HER2 agents to propose that immune escape within the tumor microenvironment is a key driver of trastuzumab resistance in HER2-positive gastric cancer.<\/jats:p>","DOI":"10.1093\/gastro\/goag068","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:28:27Z","timestamp":1782851307000},"source":"Crossref","is-referenced-by-count":0,"title":["Tumor-microenvironment-mediated immune escape drives trastuzumab resistance in HER2-positive gastric cancer"],"prefix":"10.1093","volume":"14","author":[{"given":"Huifang","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center for of Intractable Digestive Tract Tumor Precision Therapy, Henan Province Engineering Technology Research Center for Digestive Tract Tumor Precision Therapy, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer , Zhengzhou 450008, Henan, P. R.","place":["China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University , Zhengzhou 450052, Henan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cancer Hospital, The First Affiliated Hospital (College of Clinical Medicine), Henan University of Science and Technology , Luoyang 471003 , Henan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center for of Intractable Digestive Tract Tumor Precision Therapy, Henan Province Engineering Technology Research Center for Digestive Tract Tumor Precision Therapy, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer , Zhengzhou 450008, Henan, P. R.","place":["China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University , Zhengzhou 450052, Henan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunduan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center for of Intractable Digestive Tract Tumor Precision Therapy, Henan Province Engineering Technology Research Center for Digestive Tract Tumor Precision Therapy, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer , Zhengzhou 450008, Henan, P. R.","place":["China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University , Zhengzhou 450052, Henan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center for of Intractable Digestive Tract Tumor Precision Therapy, Henan Province Engineering Technology Research Center for Digestive Tract Tumor Precision Therapy, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer , Zhengzhou 450008, Henan, P. R.","place":["China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University , Zhengzhou 450052, Henan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center for of Intractable Digestive Tract Tumor Precision Therapy, Henan Province Engineering Technology Research Center for Digestive Tract Tumor Precision Therapy, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer , Zhengzhou 450008, Henan, P. R.","place":["China"]},{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University , Zhengzhou 450052, Henan, P. R.","place":["China"]},{"name":"Cancer Hospital, The First Affiliated Hospital (College of Clinical Medicine), Henan University of Science and Technology , Luoyang 471003 , Henan, P. 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