IFN-γ-resistant HLA class I-positive melanoma metastases can evolve into HLA class I-negative lesions characterized by complete insensitivity to CD8 + T-cells due to the coordinated silencing of genes involved in antigen presentation, such as HLA-B, HLA-C, B2M, TAP1, and TAP2. Most notably, mutations affecting IFN-γ signaling-related genes were also found in primary tumors, although with a substantially lower frequency than in metastases [123]. This evidence concerns the gene B2M and melanoma.