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Treatment with systemic Flt3L and CD40 agonists restored cDC number and function in murine models and clinical trial samples from patients with PDAC. CD40 agonism alone did not fully activate cDCs; however, when combined with Flt3L, dual therapy triggered a cDC-driven type I immune response characterized by T cell infiltration, interleukin-12 production, and reciprocal interferon-\u03b3 (IFN-\u03b3) responses. In mice, cDC1s were responsible for CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell expansion, and in turn, T cell\u2013derived IFN-\u03b3 enhanced cDC1 survival. Nevertheless, Flt3L and CD40 agonism increased regulatory T cells through the activation of cDC2s, dampening immunity. These findings advocate further exploration of DC-centered approaches to enhance antitumor immunity in PDAC.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adp3978","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T17:58:07Z","timestamp":1755280687000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":30,"title":["Combined Flt3L and CD40 agonism restores dendritic cell\u2013driven T cell immunity in pancreatic cancer"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-0695","authenticated-orcid":true,"given":"Graham D.","family":"Hogg","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-0263","authenticated-orcid":true,"given":"Alyssa 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