Along this line, the ongoing NIBIT-M4 clinical study, testing the immunologic and clinical efficacy of guadecitabine combined with the anti-CTLA-4 mAb, ipilimumab, in metastatic melanoma patients (Di Giacomo et al., 2018), will provide further support to the therapeutic potential of epigenetically based immunotherapy. This evidence concerns the gene CTLA4 and metastatic melanoma.