Stat5a sobers up inTOXicated T cells

Exhausted T cells are largely hampered by epigenetically enforced mechanisms that limit their effector potential. In this issue of Immunity, Beltra et al. found that Stat5 can alter these epigenetic profiles when T cells transition from the Tpex precursor stage into differentiated cells. At this stage, enforced Stat5 expression increases the number of intermediate exhausted T cells and induces durable effector cells with superior anti-tumor activity. Exhausted T cells are largely hampered by epigenetically enforced mechanisms that limit their effector potential. In this issue of Immunity, Beltra et al. found that Stat5 can alter these epigenetic profiles when T cells transition from the Tpex precursor stage into differentiated cells. At this stage, enforced Stat5 expression increases the number of intermediate exhausted T cells and induces durable effector cells with superior anti-tumor activity. Stat5 opposes the transcription factor Tox and rewires exhausted CD8+ T cells toward durable effector-like states during chronic antigen exposureBeltra et al.ImmunityDecember 12, 2023In BriefReversing CD8+ T cell exhaustion is a major challenge of cancer immunotherapy. Yet, the epigenetic stability of the exhaustion program remains a key hinderance. Beltra et al. identify the transcription factor Stat5 as a key axis to exploit for rewiring exhausted CD8+ T cells toward more durably protective states. Full-Text PDF