For instance, mutations in the interferon signaling pathway genes JAK1/2, B 2M, IFNGR1, IFNGR2, and APLNR indicate that patients with melanoma are resistant to immunotherapy (35, 36); mutations in genes related to the DDR pathway, such as POLE, POLD1, MLH1, MSH2, PMS2, MSH6, BRCA1, BRCA2, TP53, PRKDC, LIG3, RAD17, RAD51C, FANCF, and ERCC1, are associated with higher TMB and improved response to ICIs (37, 38). This evidence concerns the gene MSH6 and melanoma.