Inhibiting MDM2 enhances RIPK3-mediated necroptosis and synergizes with immune checkpoint blockade therapy

T cell infiltration, leading to improved tumor control. In immunologically "cold" tumor models, combining MDM2 inhibition with anti-PD-1 blockade converted tumors to a T cell-inflamed state and significantly improved therapeutic efficacy, even in p53-deficient settings. These findings identify MDM2 as a regulator of TNF-α-induced necroptosis and highlight its potential as a therapeutic target for cancer immunotherapy.