CTLA4 and melanoma: To test the potential relevance of DNA methylation classes in a therapeutic setting we used RRBS in an independent cohort of n = 28 pre-therapy lesions from Stage III-IV melanoma patients treated with adjuvant a-PD-1 and/or a-CTLA-4 ICB (Supplemental Table S2). The EPICA cohort samples were used as training set to classify the pre-adjuvant lesions into the DEM, LOW, INT and CIMP classes (Supplemental Table S2). We performed the subsequent analyses by merging the CIMP and INT, and the LOW and DEM subtypes.