HLA-C and neoplasm: One of the major roadblocks to the efficacy of ICIs in MSS GI cancers is that they are poorly immunogenic with a low tumor mutation burden (TMB) (< 50/genome).[30] It is known that a high TMB is associated with increased neoantigens that can be presented by major histocompatibility complexes (MHC) on tumor cells,[31] resulting in immune recognition and cytotoxic T cell responses.