In this regard, Ascierto and colleagues demonstrated significantly higher baseline Treg levels for stage III vs. stage IV disease and early recurrence vs. no recurrence in melanoma patients treated in adjuvant with high-dose IFN-α2b (42), indicating that this subset plays a key role in the response to IFN-α, whose mechanism of action relies indeed more on an indirect immunoregulatory mechanism (27) (which can be hampered by Tregs) rather than on a direct anti-tumor effect. This evidence concerns the gene IFNA2 and melanoma.