B2-microglobulin (β2M) is essential in stabilizing cell surface expression of HLA class I. Studies suggested that genomic alterations in B2M were related to both primary and acquired resistance to ICIs in some solid tumors, including melanoma and lung cancer (Gettinger et al., 2017; Sade-Feldman et al., 2017; Betof Warner et al., 2019; Lei et al., 2020). The gene discussed is B2M; the disease is melanoma.