Immune agonists—targeting STING, TLR, CD40, and OX40 pathways—fundamentally potentiate PD-1 blockade efficacy by reprogramming immunosuppressive tumor microenvironments, converting immunologically “cold” tumors into T cell-inflamed niches through dendritic cell activation, enhanced antigen presentation, and cytotoxic lymphocyte recruitment. Here, TNFRSF4 is linked to neoplasm.