CD8A and neoplasm: (1) They are poorly immunogenic because of their low tumor mutation burden; (2) frequent activation of the WNT/β-catenin signaling pathway excludes intratumoral CD8+ T cell immunity; (3) the tumor microenvironment is immunosuppressive because of the presence of various immunosuppressive cells, including tumor-associated macrophages and regulatory T cells; and (4) frequent liver metastasis in MSS mCRC may reduce the efficacy of ICIs.