CD4 and cancer: TNFRSF9+ Treg cells emerge through a trajectory from the resting Treg state to the activated state, accompanied by increased interferon responses and the upregulation of transcription factors such as HIVEP1. These CD4+ T-cell changes are observed across cancer types and represent common differentiation pathways, although their abundance and prominence vary depending on the tumor type and microenvironmental cues, such as TGF-β signaling, type I interferons, and specific tumor mutations [7].