IL2 and melanoma: IL-2 is documented as a potent activator of both CD8+T cells and NK cells through the binding to the heterotrimeric receptor consisting of three subunits including α, β, and γ.367,368 In 1998, high-dose IL-2 was approved for melanoma treatment and obtained a considerable objective response in 15–20% patients with advanced melanoma.369 However, the increased risk of severe adverse effects including capillary, leak syndrome, gastrointestinal side effects, fever and chills limited the continuous usage of IL-2 to prolong the survival of patients.