The expression of PD-L1 in melanoma cells is mainly regulated by IFN-γ signaling through the JAK1/2-STAT2/3-IRF1 axis, whereas PD-L2 is regulated by IFN-β and IFN-γ through both IRF1 and STAT3, which bind directly to PD-L2 promoters and promote immunosuppression (78).The upregulation of IFN-γ signaling with HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, NCAM1 genes popping up was also observed in our analysis of early progressors vs. long responders in gene cluster 5 as shown in Figure 3A’. Here, IRF1 is linked to melanoma.