Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma

Immunity. 2021 Sep 14;54(9):2117-2132.e7. doi: 10.1016/j.immuni.2021.08.019.

Abstract

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

Keywords: CD69; CD8 T cells; CXCR6; Cancer; TCR; TRP-2; Trm; parabiosis; scRNA-seq; vitiligo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Humans
  • Immunologic Memory / immunology*
  • Lymph Nodes / immunology*
  • Melanoma / immunology*
  • Melanoma, Experimental / immunology*
  • Mice
  • Skin Neoplasms / immunology*
  • Vitiligo

Supplementary concepts

  • Melanoma, Cutaneous Malignant