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

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.

• Authors: Jichang Han, Yanding Zhao, Keisuke Shirai, Aleksey Molodtsov, Fred W Kolling, Jan L Fisher, Peisheng Zhang, Shaofeng Yan, Tyler G Searles, Justin M Bader, Jiang Gui, Chao Cheng, Marc S Ernstoff, Mary Jo Turk, Christina V Angeles
• Journal: Nature cancer (Nat Cancer) Vol. 2 Issue 3 Pg. 300-311 (03 2021) ISSN: 2662-1347 [Electronic] England
• PMID: 34179824 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors

Topics

• CD8-Positive T-Lymphocytes (pathology)
• Humans
• Immunologic Factors
• Immunologic Memory
• Immunotherapy
• Melanoma (therapy)
• Memory T Cells