Leveraging cDC1 biology and function for enhanced immunotherapy

Conventional type 1 dendritic cells (cDC1s) promote antitumor immunity through efficient cross-presentation of tumor antigens and production of key mediators. Crucially, in the tumor microenvironment, cDC1s orchestrate immune hubs and signaling axes that support T cell responses and are associated with improved patient outcomes. During tumor progression, however, cDC1 activity is increasingly constrained by immunosuppressive signals and inhibitory cellular interactions. Many immunotherapies, including immune checkpoint blockade and adoptive cell transfer, depend on functional cDC1 populations for optimal efficacy, underscoring the need to define both the mechanisms that enable cDC1-mediated immunity and those that suppress it. Emerging strategies aim to harness cDC1s by expanding their numbers, reprogramming suppressed DC states, or strengthening interactions with CD8+ and CD4+ T cells and natural killer cells. Here, we discuss the molecular pathways, cellular phenotypes, and spatial features that govern cDC1 function, highlight the prognostic and predictive value of cDC1-associated signatures, and evaluate therapeutic approaches that leverage cDC1 biology to improve cancer treatment and durability of response.