A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.

ABSTRACT: Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of

SUBMITTER: Singer M 

PROVIDER: S-EPMC5019125 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature