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While manganese (Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ) enhances cGAS sensitivity to DNA, the precise mechanisms and potential of Mn\u2010DNA complexes in this process are unclear. Here, this work introduces a strategy to encapsulate Mn\u2010DNA complexes into DC\u2010derived immunogenic extracellular vesicle (EV\n                    <jats:sub>DC<\/jats:sub>\n                    @Mn\u2010DNA) to trigger robust anti\u2010tumor immunity. This work shows that Mn\n                    <jats:sup>2+<\/jats:sup>\n                    induces tumor cell\u2010DNA transition to Z\u2010DNA, strengthening cGAS binding and promoting its phase condensation for optimal activation in DCs. Using this newly developed Raft\u2010Ultra method, this work engineers immunogenic EVs derived from tumor cell lysate\u2010pulsed DCs, loaded with Mn\u2010DNA complexes (EV\n                    <jats:sub>DC<\/jats:sub>\n                    @Mn\u2010DNA). These EVs efficiently deliver Mn\u2010DNA complexes to DCs, activating the cGAS\u2010STING pathway both in vitro and in vivo. In animal models, EV\n                    <jats:sub>DC<\/jats:sub>\n                    @Mn\u2010DNA administration enhances vascular function, as evidenced by increased blood flow and perfusion, improved anti\u2010PD\u2010L1 delivery, reduced hypoxia, and elevated endothelial cell\u2010ICAM1 expression, which facilitates T cell adhesion. This approach expands the intratumoral population of activated DCs and T cells and promotes the formation of larger tertiary lymphoid structures, ultimately suppressing orthotopic pancreatic tumor growth. Overall, this EV\n                    <jats:sub>DC<\/jats:sub>\n                    @Mn\u2010DNA strategy reprograms intratumoral DCs, restores vascular\u2010immune homeostasis, and potentiates anti\u2010tumor immunity in pancreatic cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.202507159","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T20:14:26Z","timestamp":1761164066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tailoring Vascular\u2010Immune Homeostasis via Manganese\u2010DNA Complex\u2010Armed Immunogenic Extracellular Vesicles for Pancreatic Cancer Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Xue","family":"Jiang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA medicine Sun Yat\u2010sen Memorial 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