Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

ABSTRACT: Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8⁺ and CD4⁺ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct fro

SUBMITTER: Wang D 

PROVIDER: S-EPMC6094952 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature