Abstract
Tissue-resident memory (TRM) 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 TRM cell differentiation and re-activation but have not been implicated in sustaining TRM cell responses. Here, we identified a novel role for dendritic cells in supporting TRM to melanoma. We showed that CD8 TRM 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 TRM cells. In addition, we determined that TRM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing TRM cells and CXCL16-expressing APCs was found to be critical for sustaining TRM cell-mediated tumor protection. These findings substantially expand our knowledge of APC functions in TRM T-cell homeostasis and longevity.
Highlights
Tissue resident memory T (TRM) cells are a unique subset of memory cells persisting at initial sites of challenge [1, 2] and are important in memory responses against viruses, bacteria, fungi and parasites [3]
We found that in contrast to LNs, CD8 Tissue-resident memory (TRM) cell aggregates contained little to no B cells, high endothelial venules, or CD4 T cells (Fig S2A and B) indicating that hair follicle–associated TRM cell clusters in melanoma-associated vitiligo (MAV)-affected skin are distinct structures from tertiary lymphoid structures (TLSs)
We describe perifollicular and interfollicular clustering of mouse and human skin CD8 TRM cells in response to melanoma, respectively, and show that persistent clustering with DCs is required for skin TRM cell maintenance and dependent on the interaction between CXCR6 and CXCL16
Summary
Tissue resident memory T (TRM) cells are a unique subset of memory cells persisting at initial sites of challenge [1, 2] and are important in memory responses against viruses, bacteria, fungi and parasites [3]. Unique properties including permanent residence in tissue and constitutive expression of inflammatory cytokines and effectors make TRM cells ideal sentinels acting as first responders to reinfection of pathogens [4]. Since their discovery, TRM cells have been identified within multiple epithelial barriers and within sites of immune privilege including the brain [5]. TRM cells adapt to their location by using local fuel sources [7] indicating that they rely heavily on the tissue environment for their long-term maintenance, leading us to determine whether specific accessory cells maintain TRM cell homeostasis within a tissue niche
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