Endogenous Glucocorticoid Signaling Regulates CD8⁺ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment.

ABSTRACT: Identifying signals in the tumor microenvironment (TME) that shape CD8⁺ T cell phenotype can inform novel therapeutic approaches for cancer. Here, we identified a gradient of increasing glucocorticoid receptor (GR) expression and signaling from naïve to dysfunctional CD8⁺ tumor-infiltrating lymphocytes (TILs). Conditional deletion of the GR in CD8⁺ TILs improved effector differentiation, reduced expression of the transcription factor TCF-1, and inhibited the dysfunctional phenotype, culminating in tumor growth inhibition. GR signaling transactivated the expression of multiple checkpoint receptors and promoted the induction of dysfunction-associated genes upon T cell activation. In the TME, monocyte-macrophage lineage cells produced glucocorticoids and genet

SUBMITTER: Acharya N 

PROVIDER: S-EPMC7682805 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature