Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion

TL;DR - This Nature study identifies ZMYND8 as a regulator that enforces terminal exhaustion in CD8+ T cells by suppressing IL-2R–STAT5 signalling. Deleting ZMYND8 restores effector-like T cell states and substantially improves antiviral and antitumour immunity.

• ZMYND8 inhibits p300-mediated transcriptional activation of Il2ra, which encodes a component of the IL-2 receptor.
• This inhibition dampens IL-2R–STAT5 signalling and promotes terminal CD8+ T cell exhaustion.
• ZMYND8 deletion shifts exhausted T cells toward effector-like states.
• Targeting ZMYND8 could provide a strategy for strengthening immune responses against chronic infections and tumours.