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

Deleting the epigenetic reader ZMYND8 in CD8+ T cells restored IL-2 receptor signalling and markedly improved antitumour and antiviral immunity in preclinical models. The authors show that ZMYND8 blocks p300-driven transcription of Il2ra (CD25), damping the IL-2R–STAT5 axis and locking cells into terminal exhaustion; its removal shifted cells towards effector-like states. The work identifies a druggable epigenetic brake that could be combined with checkpoint blockade or adoptive cell therapy, although the data are mouse and cell-based with no clinical testing yet.