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To report the 3\u2010year follow\u2010up data are aimed from a novel clinical trial. This is a prospective single\u2010arm phase II trial. Patients with LAGC received neoadjuvant tislelizumab plus SOX before surgery. Biopsies are obtained before treatment, and tumor samples post\u2010treatment underwent single\u2010cell RNA sequencing (scRNA\u2010seq). Spatial transcriptomics is conducted for validation. Cox regression models and Kaplan\u2013Meier analysis are applied. A total of 49 patients are enrolled, and the median progression\u2010free (PFS) and overall survival (OS) are not achieved. The 3\u2010year PFS and OS rates are 64.1% and 73.2%, respectively. scRNA\u2010seq of 22, 248 cells from tumors from seven patients with LAGC enabled annotation of three cancer\u2010associated fibroblast (CAF) phenotypes. Spatial transcriptomics of gastric cancer samples validate the classification, showing inflammatory CAFs (iCAFs) negatively correlated with immunotherapy efficacy. Patients with LAGC show a favorable prognosis after neoadjuvant tislelizumab plus SOX treatment. CAF heterogeneity is crucial for patients with gastric cancer undergoing immunotherapy, and iCAFs is associated with an immunosuppressive microenvironment during PD\u20101 blockade with SOX therapy and validated by in vitro experiments. Patients with LAGC with higher iCAF scores are resistant to SOX PD\u20101 blockade.<\/jats:p>","DOI":"10.1002\/advs.202508433","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T07:07:28Z","timestamp":1764659248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Three\u2010Year Follow\u2010Up of Neoadjuvant Tislelizumab with Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Revealing Cancer\u2010Associated Fibroblast Heterogeneity Corresponding to PD\u20101 Blockade Efficacy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8131-1999","authenticated-orcid":false,"given":"Yao","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei Province 430022 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