Combined with the results of the current analysis that Macro_APOE/CTSZ interacts with Treg and is mutually exclusive with T effector cells in CRC‐MMRp, which may indicate that immunosuppressive microenvironment induced by interaction Macro_APOE/CTSZ and Treg may be linked to a low mutation load and deactivating immune system in CRC‐MMRp but not in CRC‐MMRd samples. This evidence concerns the gene APOE and colorectal carcinoma.