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In this study, we identified a negative immune regulatory mechanism, whereby mRNA vaccination induces programmed death\u2010ligand 1 (PD\u2010L1) expression in dendritic cells (DCs) through type I interferon (IFN\u2010I) signaling. Elevated PD\u2010L1 expression impairs T\u2010cell priming in lymph nodes through engagement of programmed death receptor 1 (PD\u20101) on T lymphocytes. To address this challenge, we developed a self\u2010cooperative RNA vaccine (SCORV) strategy by co\u2010delivering antigen\u2010encoding RNA and small interfering RNA against PD\u2010L1 (siPD\u2010L1) within a single lipid nanoparticle (LNP). Through iterative screening of &gt;300 ionizable lipids, we optimized a DC\u2010targeted LNP formulation with high RNA delivery efficiency and minimal immunotoxicity. SCORV simultaneously suppresses PD\u2010L1\u2013mediated immune resistance during antigen presentation and enhances T cell priming while alleviating T cell exhaustion. Importantly, SCORV potentiates the tumor reactivity of adoptively transferred tumor\u2010infiltrating lymphocytes and elicits robust antitumor immunity in murine melanoma and hepatocellular carcinoma models. This work highlights a rational design principle for mRNA vaccines that self\u2010correct vaccination\u2010induced immune resistance.<\/jats:p>","DOI":"10.1002\/adma.202518422","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:57:46Z","timestamp":1783666666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Self\u2010Cooperative RNA Vaccine Mitigates Dendritic Cell\u2013Mediated Acquired Immune Resistance to Potentiate Cell Therapy for Solid Tumors"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-9174","authenticated-orcid":false,"given":"Lujia","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Biology &amp; Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing 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