Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion.
- Open access
Targeting ZMYND8 enhances IL-2 signaling, promoting effector-like CD8+ T cell responses and improving antiviral and antitumor immunity.
- Why it matters: Overcoming T cell exhaustion is crucial for effective treatments of chronic infections and cancers, yet the epigenetic mechanisms suppressing IL-2 signaling remain unclear.
- What they did: Using in vivo single-cell CRISPR screens, researchers identified ZMYND8 as an epigenetic regulator that inhibits IL-2R-STAT5 signals by repressing p300 activity at the Il2ra gene locus, and they tested ZMYND8 deletion effects on T cell function.
- The result: ZMYND8 deficiency boosted IL-2 receptor expression and effector-like T cell differentiation, leading to significantly improved antiviral and antitumor responses, especially when combined with IL-2 therapy or immune checkpoint blockade.