As it was previously demonstrated by Kleffel et al., overexpression of PD-1 in exceptionally aggressive melanoma subpopulations facilitated tumor progression by activating the mTOR signaling pathway (actually, this response was highly unexpected compared to that of the classic PD-1:PD-L1 dependent T-cell anergy, a crucial aspect of immunotherapy in the clinics) (15). This evidence concerns the gene PDCD1 and melanoma.