Therefore, PD-1high Eomeshigh T cells expressing the whole panel of inhibitory receptors became exhausted upon engagement with IFN-induced ligands harbored by tumor cells, unless interventions on the tumor cell bottlenecks JAK1/JAK2 down-regulated the cascade culminating in surface expression of inhibitory ligands on tumor cells.47Ifit and Mx1, when considered as a two-feature metagene, together with non-synonymous single nucleotide variant load, were the most relevant genomic features associated with resistance to PD-1 blockade in 27 melanoma patients. This evidence concerns the gene IFNA1 and melanoma.