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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 06, 2021
Source ID
10.26508/lsa.202101056

Entities

People

  • Aleksey Molodtsov
  • Bruce R Branchini
  • Christina Angeles
  • Jennifer L Vella
  • Mary Jo Turk
  • Yina H Huang

Organizations

  • Air Force Office of Scientific Research
  • Connecticut College
  • Dartmouth–Hitchcock Medical Center
  • Geisel School of Medicine
  • National Institutes of Health
  • Norris Cotton Cancer Center
  • University of Michigan

Tags

Fields of Study

  • Biology

Readers

  • Military Engineering.
  • Molecular Biology and Genetics
  • Molecular and Cellular Biology