Fig. 9: Signal pathway of HCC immune evasion mediated by O₂^•− in HSCs.

HSCs produce large amounts of O₂^•− upon activation. Excessive O₂^•− damages the active region of CDK, preventing CDK4 from phosphorylating downstream FZR1. Unphosphorylated FZR1 prevents SPOP from degrading PD-L1, which raises PD-L1 levels.