In the NIBIT-M4 (Italian Network for Tumor BIoTherapy – Metastatic Melanoma) trial, a phase 1b study of the DNA hypomethylating agent guadecitabine with ipilimumab, the ORR was 26%, with tumor immune contexture showing an increase in CD8+, PD-1+ T-cells in post-treatment tumors [72]. This evidence concerns the gene CD8A and neoplasm.