IRF8 and melanoma: The methylation of IRF1, IRF2, IRF5, and IRF8 transcription factor promoters was significantly higher in the StemnessHIGH/ImmuneLOW melanoma patients (p < 0.0001) (Figure 6E), suggesting that epigenetic silencing of interferon-inducible signaling ultimately results in the acquisition of melanoma stem cell-like phenotype.