biostudies-literatureChen BHebei Provincial Major Science and Technology Support Plan International Scientific and Technological Cooperation/Hong Kong, Macau, and Taiwan Science and Technology Cooperation ProjectCUHK Direct Research GrantNational Natural Science Foundation of ChinaRGC Postdoctoral Fellowship Schemethe NSFC-RGC Joint Research Scheme282https://www.ebi.ac.uk/biostudies/studies/S-EPMC12590883biostudies-literatureUnknown24(1)<h4>Background</h4>Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, yet their spatial organization and immunomodulatory functions in H. pylori-associated gastric cancer (GC) remain incompletely understood.<h4>Methods</h4>We profiled formalin-fixed paraffin-embedded (FFPE) tumors from 71 GC patients using spatial transcriptomics and integrated single-cell RNA-seq from three independent cohorts (China, USA, and Singapore). CAF-immune cell colocalization was quantified by neighborhood enrichment and aggregation index score. Ligand-receptor inference and trajectory analysis resolved CAF signaling and state transitions. To delineate post-transcriptional control, ARE-motif scanning and expression correlations were combined with laser-assisted crosslinking anMolecular cancerSpatial and functional dissection of cancer-associated fibroblasts-mediated immune modulation in H. pylori-associated gastric cancer.PMC12590883N_CUHK448/23822729902024.0668240301725297706DUGC/GEN/562/3Wu JZhang FLiu JDong YYu PLyu YFang CWong CCCheung JCTYu JTang HTo KFXie FWang SCheung AHKWang ZZheng XWu WKKKang WTong MLeung KTLu CBurgermeister EChen BZhang YTian RFeng TXu YfalseSpatial and functional dissection of cancer-associated fibroblasts-mediated immune modulation in H. pylori-associated gastric cancer.<h4>Background</h4>Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, yet their spatial organization and immunomodulatory functions in H. pylori-associated gastric cancer (GC) remain incompletely understood.<h4>Methods</h4>We profiled formalin-fixed paraffin-embedded (FFPE) tumors from 71 GC patients using spatial transcriptomics and integrated single-cell RNA-seq from three independent cohorts (China, USA, and Singapore). CAF-immune cell colocalization was quantified by neighborhood enrichment and aggregation index score. Ligand-receptor inference and trajectory analysis resolved CAF signaling and state transitions. To delineate post-transcriptional control, ARE-motif scanning and expression correlations were combined with laser-assisted crosslinking an2025-01-01T00:00:00Z2025 Nov2026-06-10T05:09:17.168Z2026-06-10T03:07:37.199ZS-EPMC125908834119411310.1186/s12943-025-02490-9