IL-2 was the first cytokine discovered to promote T cell proliferation and expansion, and recombinant IL-2 (rIL-2) was the first immunotherapeutic that as monotherapy reproducibly induced durable, complete, and in some patients, curative regression of metastatic malignancies (melanoma and renal cancer).189,190 However, high-dose rIL-2 can cause severe life-threatening adverse effects such as capillary leakage, limiting its clinical application. This evidence concerns the gene IL2 and melanoma.