HCC demonstrates this subtlety: whereas PSMB8 is induced and prognostically relevant, with single-cell measurements confining expression to adaptive immune compartments and tissue confirmation supporting an increase in tumor, its association with immune checkpoints (e.g., Programmed death-ligand 1 (PD-L1)) suggests concomitant engagement of immune-evasion circuits such that simplistic “high-is-good” heuristics are challenging (59). This evidence concerns the gene PSMB8 and hepatocellular carcinoma.