Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified and characterized a new subset, the DC3s, expressing CD88–CD1c+CD163+ DCs as immediate precursors of inflammatory DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of classical DCs and monocytes. Like classical DCs but unlike monocytes, DC3s drive activation of naive T cells. In vitro, DC3s display a distinctive ability to prime CD8+ T cells expressing tissue-resident memory T cell (TRM) phenotype and transcriptomic signature. In vivo, DC3s infiltrate luminal breast cancer and their infiltration correlated positively with TRM in these primary tumors.
Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.