These findings collectively position E2F hyperactivity as a dual driver of proliferative advantage and immune evasion in high-risk neuroblastoma, suggesting that therapeutic strategies combining CDK4/6 inhibitors (to target E2F activation) with NK cell engagers or TIM-3 blockade (to overcome immune suppression) may be particularly effective, as recently demonstrated in preclinical models of E2F3-amplified neuroblastoma (20). Here, HAVCR2 is linked to neuroblastoma.