For instance, dMMR/MSI-H CRC patients with low TMB, immunosuppressive tumor microenvironment, or mutation in the PTEN gene or PIK3CA gene are resistant to ICIs (51, 52), while pMMR/MSS CRC patients with a mutation in POLE or POLD1 gene are sensitive to ICIs (53). Here, POLE is linked to colorectal carcinoma.