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.

Automated summary

Dendritic cells play a crucial role in supporting T-RM responses to melanoma, with their close interaction being essential for maintaining immune protection. Chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis are critical for T-RM migration and persistence in the skin, with the interaction between CXCR6-expressing T-RM cells and CXCL16-expressing APCs being pivotal for sustaining T-RM cell-mediated tumor protection.