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MiR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigentic reprogramming T cell fate

ABSTRACT: T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here, we show that miR-155 increased CD8+ T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. miR-155 enhanced 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 orchestrated a transcriptional program extensively shared with miR-155 to restrain T cell senescence and sustain CD8+ T cell antitumor responses. These effects relied on Phf19 histone-binding capacity, which is critical for PRC2 recruitment to chromatin. These findings establish the miR-155–Phf19–PRC2 as a pivotal axis regulating CD8+ T cell differentiation, paving new ways for potentiating cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate.

ORGANISM(S): Mus musculus

PROVIDER: GSE128664 | GEO | 2019/03/29

REPOSITORIES: GEO

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miR-155 enhances PRC2 activity via polycomb-like protein Phf19 to sustain T cell antitumor immunity [ChIP-Seq]

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