Intriguingly, studies have shown that patients with HP and those who achieve complete response (CR) after ICB therapy exhibit similar levels of tumor-infiltrating CD8 + T cells and an IFN-γ gene signature.341 First, IFN-γ has been shown to upregulate MDM2/4, further impairing P53 activity.342,343 In addition, patients with HP but not CR exhibit elevated expression of FGF2 and β-catenin signaling in tumors.341 Mechanistically, CD8 + T cell-derived IFN-γ targets FGF2 to selectively inhibit PKM2, a key enzyme in glycolysis, leading to reduced NAD+ production and increased β-catenin activity. The gene discussed is CD8A; the disease is neoplasm.