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

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.