Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy

Nat Cancer. 2021 Mar;2(3):300-311. doi: 10.1038/s43018-021-00180-1. Epub 2021 Mar 24.

Abstract

While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8+ T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (TRM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as TRM in skin and as effector memory T (TEM) cells in blood. Clonotypes that dispersed throughout tumor, skin, and blood preferentially expressed a IFNG / TNF-high signature, which had a strong prognostic value for melanoma patients. Remarkably, clonotypes from tumors were found in patient skin and blood up to nine years later, with skin maintaining the most focused tumor-associated clonal repertoire. These studies reveal that cancer survivors can maintain durable memory as functional, broadly-distributed TRM and TEM compartments.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Humans
  • Immunologic Factors
  • Immunologic Memory
  • Immunotherapy
  • Melanoma* / therapy
  • Memory T Cells*

Substances

  • Immunologic Factors