Contextual control of CD8+ T cell priming by dendritic cell subsets in tumor and inflammatory microenvironments.

Migratory and lymph node-resident dendritic cells occupy distinct niches and drive T cell activation during infection, vaccination, and cancer. How tissue context and dendritic cell subset-specific transcriptional programs integrate to shape CD8+ T cell priming remains incompletely defined. Using fluorescent antigen, we track antigen distribution, dendritic cell transcriptional programming, and cross-presentation across tumor, inflamed, and steady-state tissues. Tumor antigen is more widely distributed among lymph node dendritic cells than skin-derived antigen. Migratory type 1 dendritic cells display higher expression of cross-presentation machinery and superior per-cell cross-presentation and induction of CD8+ T cell proliferation compared to lymph node-resident type 1 dendritic cells. Ultimately, antigen access and cell-specific cross-presentation efficiency together predict the quality of CD8+ T cell priming. These results identify migratory type 1 dendritic cells as central mediators of antitumor CD8+ T cell responses and support therapeutic strategies that augment the efficiency of resident dendritic cell cross-presentation.