NR0B2 and neoplasm: Additionally, PD-1 binding to PD-L1 inhibits both NK cell degranulation and IFN-γ secretion, activates SHP phosphatase, and suppresses phosphorylation within the PI3K–AKT pathway, thereby blocking the cytotoxic function of NK cells (47).Blocking PD-L1 enhances the anti-tumor activity of NK cells and increases tumor clearance rates (48), although some models rely on T cell cooperation.