Helicobacter pylori-Induced Inflammatory Cancer Transformation Microenvironment Drives Gastric Carcinogenesis

作者：Yufei Fu, Jing Tong, Manxuan Zhu, Liuyi Xu, Fengming Huang, Yixin Zhang, Xinyue Wang, Zhejiong Wang, Jingcheng Zhang, Jinjing Lv, Tao Jiang, Bin Lv, Guangji Zhang · 发表于：Cellular and Molecular Gastroenterology and Hepatology · 年份：2026 · DOI：10.1016/j.jcmgh.2026.101757 · 被引用次数：4 · 研究领域：Helicobacter pylori-related gastroenterology studies、Cancer Mechanisms and Therapy、Cancer Research and Treatments

BACKGROUND & AIMS: Helicobacter pylori (H pylori) eradication significantly reduces gastric cancer risk but offers limited benefit for patients with advanced atrophic gastritis. After eradication, a persistent inflammatory-cancer-transformation microenvironment (ICTM) drives gastric carcinogenesis, warranting further investigation. METHODS: We constructed a single-cell atlas of 22 gastric antral mucosae across disease stages, including normal controls, H pylori-infected non-atrophic gastritis, H pylori-infected chronic atrophic gastritis, and post-eradication chronic atrophic gastritis (stratified by pathological improvement). Key findings were validated via multiplex immunofluorescence and primary cancer-associated fibroblast (CAF) experiments. RESULTS: iCAF3 are enriched in infected tissues and persist in post-eradication patients with CAG. H pylori infection reprograms iCAFs, leading to extracellular matrix reorganization and senescence with senescence-associated secretory phenotype. This reprogramming promotes epithelial malignant transformation and stemness. Infection-driven reprogramming of the iCAF-epithelial niche is accompanied by an immunosuppressive state after eradication. CONCLUSIONS: H pylori infection induces persistent ICTM after eradication. Infection-driven iCAF differentiation contributes to epithelial malignant transformation and a potential immunosuppressive microenvironment, linking to gastric carcinogenesis. Our findings underscore the critical role of ...