Subsets of exhausted CD8⁺ T cells differentially mediate tumor control and respond to checkpoint blockade.

ABSTRACT: T cell dysfunction is a hallmark of many cancers, but the basis for T cell dysfunction and the mechanisms by which antibody blockade of the inhibitory receptor PD-1 (anti-PD-1) reinvigorates T cells are not fully understood. Here we show that such therapy acts on a specific subpopulation of exhausted CD8⁺ tumor-infiltrating lymphocytes (TILs). Dysfunctional CD8⁺ TILs possess canonical epigenetic and transcriptional features of exhaustion that mirror those seen in chronic viral infection. Exhausted CD8⁺ TILs include a subpopulation of 'progenitor exhausted' cells that retain polyfunctionality, persist long term and differentiate into 'terminally exhausted' TILs. Consequently, progenitor exhausted CD8⁺ TILs are better able to control tumor growth t

SUBMITTER: Miller BC 

PROVIDER: S-EPMC6673650 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature