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

Aleksey K. Molodtsov, Nikhil Khatwani, Jennifer L. Vella, Kathryn A. Lewis, Yanding Zhao, Jichang Han, Delaney E. Sullivan, Tyler G. Searles, Nicholas K. Preiss, Tamer B. Shabaneh, Peisheng Zhang, Aaron R. Hawkes, Brian T. Malik, Fred W. Kolling, Edward J. Usherwood, Sandra L. Wong, Joseph D. Phillips, Keisuke Shirai, Christina V. Angeles, Shaofeng YanTyler J. Curiel, Yina H. Huang, Chao Cheng, Mary Jo Turk

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2117-2132.e7
JournalImmunity
Volume54
Issue number9
DOIs
StatePublished - Sep 14 2021
Externally publishedYes

Keywords

  • Cancer
  • CD69
  • CD8 T cells
  • CXCR6
  • parabiosis
  • scRNA-seq
  • TCR
  • Trm
  • TRP-2
  • vitiligo

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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