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In this study, we utilized neoantigens, lipopolysaccharide and IFN\u2010\u03b3 to induce the maturation of DCs, and then isolated DEVs derived from these mature DCs. We showed that the immune checkpoint inhibitor (anti\u2010CTLA\u20104 antibody, aCTLA\u20104) can improve the immunostimulatory function of DEVs by directly activating T cells through immune checkpoint signal blockade. The cytokine interleukin\u201012 (IL\u201012), as one of the third signals for T cell activation, can also enhance the capability of DEVs to activate T cells directly. Based on these findings, we designed the engineered DEVs conjugated with IL\u201012 and aCTLA\u20104 (DEV@IL\u201012\u2010aCTLA\u20104) to improve the therapeutic potential of DEVs by providing sufficient immune regulatory signals. Moreover, the carrier property of DEVs also contributes to the delivery of IL\u201012 and aCTLA\u20104 to lymph nodes. This indicates that the conjugation of DEVs with IL\u201012 and aCTLA\u20104 constitutes a complementary approach, where IL\u201012 and aCTLA\u20104 help to enhance the T cell activation effect of DEVs, and DEVs facilitate the delivery of IL\u201012 and aCTLA\u20104. Our results showed that DEV@IL\u201012\u2010aCTLA\u20104 can enhance the Th1 immune response and reverse exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the tumour microenvironment, effectively inducing robust T cell immune responses and inhibiting tumour growth in tumour\u2010bearing mice. Overall, this study expands the theoretical foundation of DEVs and provides a universal strategy for optimizing cancer combination immunotherapy by reprogramming DEVs.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70068","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T09:51:53Z","timestamp":1745661113000},"source":"Crossref","is-referenced-by-count":22,"title":["Dendritic Cell Derived\u2010Extracellular Vesicles Engineered to Express Interleukin\u201012 and Anti\u2010CTLA\u20104 on Their Surface for Combinational Cancer Immunotherapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiangbin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, and NHC Key Laboratory of Pulmonary Diseases Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"Hubei 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