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In mouse models of checkpoint inhibitor\u2013resistant pancreatic cancer, coactivation of Dectin-1, via systemic \u03b2-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Antitumor activity was dependent on cDC1s and T cells but did not require classical T cell\u2013mediated cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell\u2013mediated IFN-\u03b3 signaling, which converged with Dectin-1 activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be invoked by coactivation of complementary myeloid signaling pathways.<\/jats:p>","DOI":"10.1126\/sciimmunol.adj5097","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T18:58:26Z","timestamp":1700247506000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":54,"title":["Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-1132","authenticated-orcid":true,"given":"Max M.","family":"Wattenberg","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 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