Genetic and epigenetic mechanisms may potentially affect all the genes involved in the antigen processing and presenting machinery, particularly the gene of the B2-microglobulin (B2M) and thereby, MHC class I. Ribas’ team showed by whole-exome sequencing that a truncating mutation in the gene encoding for B2M led to loss of surface expression of MHC class I, which in turn resulted in loss of response to ICI in melanoma patients[42]. The gene discussed is B2M; the disease is melanoma.