Since the initial report describing OX40 expression on tumor-infiltrating T-cells in melanoma and head and neck cancer patients [222], the therapeutic targeting of the OX40L/OX40 axis for cancer therapy has been pursued using agonistic OX40 antibodies or recombinant forms of soluble OX40L (e.g., OX40L:Fc) (Figure 9) [131, 223]. This evidence concerns the gene TNFRSF4 and melanoma.