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Surface markers were validated via immunofluorescence, immunohistochemistry, and flow cytometry. The role of the identified CAF subset was examined using in vitro co-culture and in vivo tumor models. Animal models were utilized to study the impact of ICAM-1\n                      <jats:sup>+<\/jats:sup>\n                      CD51\n                      <jats:sup>+<\/jats:sup>\n                      CAFs on CRC tumor growth and immune cell infiltration. Cytokine array profiling, western blotting, and bioinformatics analyses were employed to explore the underlying signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a functionally enriched CAF subset defined by co-expression of ICAM-1 and CD51 (ICAM-1\u207aCD51\u207a CAFs), which exhibits potent monocyte-recruiting capacity and drives monocytes to acquire M2-like tumor-associated macrophages (TAMs) and monocytic myeloid-derived suppressor cells (M-MDSCs) associated phenotype and suppressive feature. In clinical CRC samples, the abundance of ICAM-1\u207aCD51\u207a CAFs correlated positively with intratumoral TAM infiltration. In vivo validation confirmed that ICAM-1\u207aCD51\u207a CAFs promote intratumoral accumulation of both TAMs and MDSCs, thereby accelerating tumor progression. Mechanistically, osteopontin (OPN) engagement of CD51 integrin activated the FAK\/p38 MAPK pathway within CAFs, enhancing secretion of key cytokines MCP-3, CXCL5, and IL-6, which orchestrate myeloid cell recruitment and differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates that ICAM-1\u207aCD51\u207a CAFs regulate cytokine secretion and contribute to myeloid cell recruitment and differentiation in CRC through the OPN\/CD51-FAK\/p38 MAPK axis. Targeting this CAF subset may represent a promising therapeutic strategy for CRC, which warrants further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08642-9","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:25:49Z","timestamp":1784255149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ICAM-1\u207aCD51\u207a CAFs drive immunosuppression in colorectal cancer via OPN-triggered chemokine secretion"],"prefix":"10.1186","volume":"24","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senrui","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1384-7369","authenticated-orcid":false,"given":"Jing","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"8642_CR1","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","volume":"394","author":"E Dekker","year":"2019","unstructured":"Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. 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All patients provided written informed consent. All animal experiments were approved by the Laboratory Animal Ethics Committee of Xuzhou Medical University (No. 202512T048). All procedures involving animals were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors contributed to the development of the manuscript and agreed to the content of the final version.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"957"}}