Our group repeatedly demonstrated aberrant methylation levels of immune checkpoint genes [i.e. PD-1, PD-L1, PD-1 ligand 2 (PD-L2), 4-1BB, LAG3, and cytotoxic T-lymphocyte associated protein 4 (CTLA4)] with a predictive and prognostic value in different malignancies including melanoma [32–38]. The gene discussed is CTLA4; the disease is melanoma.