{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:52:45Z","timestamp":1789602765341,"version":"build-2803163510"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"12","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007278","name":"Henry Ford Health System","doi-asserted-by":"publisher","award":["H10409"],"award-info":[{"award-number":["H10409"]}],"id":[{"id":"10.13039\/100007278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["1258569"],"award-info":[{"award-number":["1258569"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA98105"],"award-info":[{"award-number":["R01CA98105"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"<jats:p>\n                    Conventional type 1 dendritic cells (cDC1s) are specialized for cross-presenting tumor antigens and determining the efficacy of immunotherapies, including immune checkpoint blockade and adoptive cell therapy. However, their rarity and tumor-induced dysfunction severely limit CD8 T cell priming and represent a central bottleneck to therapeutic efficacy. While strategies such as anti\u2013DEC-205-mediated antigen delivery and Flt3L-driven DC expansion can enhance host DC function, their reliance on functional cDC1s remains a significant constraint. We developed Tim-3-targeted vaccines by conjugating tumor antigens or neoantigens to anti\u2013Tim-3 antibodies. These vaccines delivered antigens to both cDC1s and cDC2s, and elicited robust, durable CD8 T cell responses. Remarkably, Tim-3-targeted vaccines endowed cDC2s with efficient cross-presentation capacity that matched that of cDC1s. In tumor-bearing mice or in CD11c-\u03b2-catenin\n                    <jats:sup>active<\/jats:sup>\n                    mice, which model \u03b2-catenin-driven DC dysfunction, Tim-3-targeted vaccination restored cross-priming and counteracted tumor- and DC-mediated immunosuppression. In Batf3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice lacking cDC1s, anti-Tim-3-based vaccines still elicited significant CD8 T cell cross-priming and tumor control\u2014albeit both were reduced compared to wild-type mice\u2014 demonstrating that cDC1s contribute to but are not essential for Tim-3-targeted vaccine\u2013induced CD8 T cell priming and anti-tumor efficacy. Strikingly, a single dose of anti-Tim-3\u2013neoantigen vaccination eradicated large established MC38 tumors in a CD8 T cell\u2013dependent manner. Together, these data identify Tim-3-targeted vaccines as a next-generation cancer vaccine platform that broadens DC engagement, reduces reliance on cDC1s, and overcomes tumor- and DC-mediated immunosuppression, addressing key limitations of current DC-based cancer vaccines.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2518080123","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:44:53Z","timestamp":1773942293000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Tim-3-targeted vaccines overcome tumor immunosuppression and reduce cDC1 dependence to elicit potent anti-tumor immunity"],"prefix":"10.1073","volume":"123","author":[{"given":"Chunmei","family":"Fu","sequence":"first","affiliation":[{"name":"Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health","place":["Detroit"]},{"name":"Immunology Program, Henry Ford Cancer Institute, Henry 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