MiR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8⁺ T cell fate.

ABSTRACT: T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8⁺ T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. miR-155 enhances Polycomb repressor complex 2 (PRC2) activity indirectly by promoting the expression of the PRC2-associated factor Phf19 through downregulation of the Akt inhibitor, Ship1. Phf19 orchestrates a transcriptional program extensively shared with miR-155 to restrain T cell senescence and sustain CD8⁺ T cell antitumor responses. These effects rely on Phf19 histone-binding capacity, which is critical for the recruitment of PRC2 to the target chromatin. These findings establish the

SUBMITTER: Ji Y 

PROVIDER: S-EPMC6517388 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature