TNF and neoplasm: Both in orthotopic melanoma and autochthonous PCa, even the combination of anti-CTLA-4 and anti-PD-1 exerted modest antitumor effects (37), and required the addition of fresh T cells (i.e., ACT) and minute amounts of TNF-α targeted to tumor-associated vessels to favor endothelial cell activation, tumor infiltration by fully effector T cells, and tumor debulking (38, 39).