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Myofibroblastic CAFs (myCAFs), the major subtype, form a tumor barrier by generating a dense extracellular matrix (ECM) that greatly limits the penetration of immune cells and promotes an immunosuppressive microenvironment. Reprogramming the immunosuppressed myCAFs into the immune activated antigen presenting CAF (apCAFs), rather than directly eliminating CAFs, is a better treatment modality. We developed a spatiotemporally\u00a0ultrasound\u2010controlled nanoparticle (mRNA\/V@M NPs) based on a lipid\u2010polymer hybrid drug delivery platform to co\u2010encapsulate CD74 mRNA and V\u20109302. Interestingly, this study found that successfully reprogrammed myCAFs could activate CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, reduce the ECM, and promote immune cell infiltration through the CD74\u2010MHC II pathway. To overcome the limitation of MHC I immunodeficiency, V\u20109302 was used to induce immunogenic cell death (ICD) in tumor cells and activate dendritic cells (DCs) to compensate for MHC I\u2010mediated immunodeficiency. In conclusion, in a fibrotic triple\u2010negative breast cancer mouse model, mRNA\/V@M NPs combined with ultrasound treatment significantly enhanced MHC I and MHC II activation and increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and suppressed immunosuppressive TME, thereby triggering robust systemic antitumor immunity.\n                  <\/jats:p>","DOI":"10.1002\/advs.76673","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:42:56Z","timestamp":1785156176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporally Ultrasound\u2010Controlled Nanoparticles Reprogramming Immunostimulatory Antigen\u2010Presenting Cancer\u2010Associated Fibroblasts to Enhance Cancer Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Chen","family":"Ai","sequence":"first","affiliation":[{"name":"Department of Radiology 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Medicine &amp; Functional Imaging Shandong University  Jinan Shandong People's Republic of China"},{"name":"National Medicine\u2010Engineering Interdisciplinary Industry\u2010Education Integration Innovation Platform Shandong University  Jinan Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3430-4817","authenticated-orcid":false,"given":"Dexin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology Qilu Hospital of Shandong University  Jinan Shandong People's Republic of China"},{"name":"Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University  Jinan People's Republic of 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