Combining the previous studies and current analysis, regulating GLUL on macrophages for changing their phenotype and further blocking interaction with Treg to alleviate the immunosuppressive microenvironment, maybe a potential combined treatment strategy with immune checkpoint treatment for CRC and LC patients with high Macro_APOE/CTSZ cell infiltration and who do not respond to immunotherapy, such as MMRp samples [17]. The gene discussed is CTSZ; the disease is colorectal carcinoma.