Since the 1980s, the anti-tumor potential of the same cytokines described above have been investigated in large-scale clinical trials for the treatment of human melanoma patients [135,136,137], leading to the FDA approval of IL-2 for cancer treatment of melanomas that are generally refractory to standard therapy, and to the extensive testing of other cytokines, including GM-CSF, IL-12, and IL-18 for patients with advanced cancer. This evidence concerns the gene IL18 and cancer.