In chronic stimulatory settings such as tumor microenvironments, sustained IL-2 signaling drives CD8+ T cell exhaustion through STAT5-mediated tryptophan hydroxylase 1 upregulation, generating 5-hydroxytryptophan that promotes inhibitory receptor expression and suppress effector function, revealing a conserved metabolic-epigenetic axis of T cell dysfunction in both mouse and human systems (104). Here, CD8A is linked to neoplasm.