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

Immunity, 2021

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 transcrip-
tional characteristics of tumor-specific CD8 + T cells were defined by the tissue of occupancy. Parabiosis re-
vealed 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, re-
stricting metastatic cancer.

iTAg Tetramer/PE – H-2 Kb TRP2 (MBL-TB-5004-1) manufactured by our partner MBL is featured in this study.