The resistance to ICB is in part due to the underlying immunosuppressive nature of the “cold” tumor, which is characterized by the low infiltration of tumor-infiltrating lymphocytes (TILs), low tumor mutational burden (TMB) and low major histocompatibility complex (MHC) class I expression in the tumor microenvironment (TME) [8, 9]. The gene discussed is HLA-C; the disease is neoplasm.