Our earlier published findings in wild type (WT), p55KO, p75KO and double p55KO/p75KO murine LLC and B16 melanoma tumor models suggest that the absence of p75 signaling in tumor tissue in vivo may deliver a “double hit” by affecting survival and function of ECs and of tumor cells, while antecedent high levels of TNF (due to an ongoing tumor necrosis) in tumor tissue could have self-destructive effect [13]. The gene discussed is TNFRSF1B; the disease is melanoma.