Taken together, these data show that DNMTi-induced DNA demethylation may be associated with an upregulation of antitumorigenic immune subpopulations and that melanoma ICAM-1high expression may be a predictive factor for an immune-permissive TME, characterized by increased infiltration of M1 macrophages, CD8+ and CD4+ T cells, and high expression of the IFN-γ gene signature. This evidence concerns the gene CD4 and melanoma.