Persistent STAT5 activation reprograms the epigenetic landscape in CD4⁺ T cells to drive polyfunctionality and antitumor immunity.

ABSTRACT: The presence of polyfunctional CD4⁺ T cells is often associated with favorable antitumor immunity. We report here that persistent activation of signal transducer and activator of transcription 5 (STAT5) in tumor-specific CD4⁺ T cells drives the development of polyfunctional T cells. We showed that ectopic expression of a constitutively active form of murine STAT5A (CASTAT5) enabled tumor-specific CD4⁺ T cells to undergo robust expansion, infiltrate tumors vigorously, and elicit antitumor CD8⁺ T cell responses in a CD4⁺ T cell adoptive transfer model system. Integrated epigenomic and transcriptomic analysis revealed that CASTAT5 induced genome-wide chromatin remodeling in CD4⁺ T cells and established a distinct epigenetic and

SUBMITTER: Ding ZC 

PROVIDER: S-EPMC8265158 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature