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Dendritic cells (DC) are gatekeepers of immunity, critical to both an initiate immune response upon infection and promote tolerance to self-antigens.
We have just established that DC subsets in the skin that constitutively migrate into LNs can individually and collectively temper an on-going immune response. Tissue DC originating in skin share a unique transcriptome signature geared towards immune dampening when compared to their lymphoid counterparts in both mouse and human.
Here we demonstrate expression of unique core skin DC transcripts are closely associated with increased clinical aggressiveness of BCC in humans and the stratify stage 4 melanoma outcomes. In mice, loss of signature genes in DC, which include but are not limited to PD-L1/PD-L2, lead to enhanced antigen-specific immunity, decreased tumor growth, and improved anti-tumor vaccine priming to melanoma skin cancer by distinguishable molecular control of T cell effector function and clonal proliferation.
These data suggest core skin DC signatures regulate the immune-epithelial interface.