BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models.

ABSTRACT: Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription facto

SUBMITTER: Kagoya Y 

PROVIDER: S-EPMC5004946 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature