While PD‐1/PD‐L1 blockade therapy has emerged as an encouraging approach for various cancers, it has not yet shown a meaningful positive outcome for MSS/pMMR CRC patients who account for 95% of metastatic CRC.[46] The high expression of mismatch repair gene in MSS/pMMR CRC leads to a decrease in tumor neoantigens and epitopes, thereby resulting in poor immunogenicity.[46] Additionally, the downregulation of MHC I further compromises antigen presenting,[62] ultimately leading to the low infiltration and dysfunction of CD8+ T cells in MSS/pMMR CRC. This evidence concerns the gene CD8A and neoplasm.