This reprogramming drives progenitor-exhausted T cell (Tpex) differentiation, as shown by: (1) IPA supplementation in breast cancer, melanoma, and CRC models synergizing with PD-1 blockade to increase CD8+ tumor-infiltrating lymphocyte (TIL) frequency and T-cell factor 1 (TCF-1) expression; (2) Tcf7 knockout abrogating IPA’s ability to enhance immunotherapy, confirming Tcf7 as a critical mediator; (3) adoptive transfer of IPA-pretreated CD8+ T cells (but not untreated cells) restoring aPD-1 responsiveness in Rag1-/- mice, with CD8 neutralization eliminating IPA’s efficacy (110). Here, CD8A is linked to melanoma.