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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 and immunoprecipitation sequencing (LACE-seq) to nominate ZFP36 targets. Immune contexture and prognostic associations were evaluated using CIBERSORT-ABS and Kaplan-Meier analyses in The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We first defined the spatial distributions of the four CAF subtypes reported in prior studies and found that their immune associations varied across histologic and infection-defined GC subtypes. In\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -positive tumors, THBS1\u207a CAFs were spatially enriched near regulatory T cells (Tregs) and were associated with local immunosuppression through WNT5-FZD interactions. In parallel, ZFP36 bound AU-rich elements within the FN1 3\u2032 untranslated region (3'UTR), destabilizing FN1 mRNA and thereby diminishing FN1\u207a CAF-mediated cytotoxic T lymphocyte (CTL) activation. Together, these axes promoted Treg accumulation and suppression of CTL activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings reveal infection-associated stromal programs that shape the immune landscape in GC and highlight CAF-directed pathways as potential therapeutic targets in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -associated GC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:bold>-induced CAF-mediated immunosuppression in GC.<\/jats:bold>\n                      1.\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection triggers transcriptional reprogramming of CAFs within the tumor microenvironment of GC. 2. The CAF subset marked by THBS1 is spatially enriched adjacent to Tregs and facilitates their recruitment via WNT5-FZD ligand-receptor signaling. 3. The RNA-binding protein ZFP36 binds AU-rich elements in the FN1 3\u2019UTR, destabilizing FN1 mRNA and thereby attenuating CTL activation. 4. The THBS1-WNT5 axis stabilizes Tregs, whereas the ZFP36-FN1 axis limits CTL activation, converging to drive local immunosuppression in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -positive GC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12943-025-02490-9","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T03:14:54Z","timestamp":1762398894000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Spatial and functional dissection of cancer-associated fibroblasts-mediated immune modulation in H. pylori-associated gastric cancer"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2430-7934","authenticated-orcid":false,"given":"Bonan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhen","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuda","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin H. 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Cells. 2019;9:27.","DOI":"10.3390\/cells9010027"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-025-02490-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12943-025-02490-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-025-02490-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T03:15:02Z","timestamp":1762398902000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/s12943-025-02490-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2490"],"URL":"https:\/\/doi.org\/10.1186\/s12943-025-02490-9","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"14 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human samples and data used in this study were obtained with approval from the relevant institutional ethics committees. The study was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2022.060). For all cohorts, the requirement for informed consent was waived due to the retrospective nature of the study and use of de-identified archival or publicly available data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent was obtained from each patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"282"}}