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Tissue-resident memory (T RM ) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. APCs promote T RM cell differentiation and re-activation but have not been implicated in sustaining T RM cell responses. Here, we identified a novel role for dendritic cells in supporting T RM to melanoma. We showed that CD8 T RM cells remain in close proximity to dendritic cells in the skin. Depletion of CD11c + cells results in rapid disaggregation and eventual loss of melanoma-specific T RM cells. In addition, we determined that T RM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing T RM cells and CXCL16-expressing APCs was found to be critical for sustaining T RM cell-mediated tumor protection. These findings substantially expand our knowledge of APC functions in T RM T-cell homeostasis and longevity.

Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells