〔Abstract〕 To investigate the effect and mechanism of M2 macrophage polarization induced by HCT116 with highly metastatic colorectal cancer cells on immune escape in colorectal cancer. Methods After the co-cul- ture of colorectal cancer cells conditioned medium (CM) and PMA-induced M0 macrophages , the polarization of M2 macrophages was observed by flow cytometry , real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay(ELISA) experiments . The CMM0 , CMSW480 -Mφ and CMHCT116 -Mφ were co-cultured with HCT116 cells , and the expression of programmed death-ligand 1 (PD-L1) was detected by Western blot and qPCR . At the same time , the stimulated HCT116 cells were co-cultured with human T lymphocytes to detect the survival of HCT116 cells and the levels of tumor necrosis factor-α ( TNF-α) and interferon-γ ( IFN-γ) . The difference of kruüppel-like factor 4 (KLF4) expression between SW480 and HCT116 cells was detected by Western blots , qPCR and ELISA . After pretreatment of HCT116 cells with KFL4 inhibitor Kenpaullone ( Ken) , the CMHCT116 and CMHCT116 + Ken were co-cultured with M0 macrophages and the polarization of M2 macrophages was observed by flow cytometry , qPCR and ELISA . The CMHCT116 -Mφ and CM (HCT116 + Ken) -Mφ was co-cultured with HCT116 cells , and the PD-L1 expression of HCT116 cells was detected by Western blot and qPCR . Results After the stimulation of M0 macrophages with CM , the proportion of CD11b + CD206 + cells in HCT116-Mφcells was higher , and the expres- sion of M2 macrophage markers interleukin (IL-10) and transforming growth factor-β(TGF-β) were higher. Com- pared with the CMSW480 -Mφ group , the PD-L1 protein expression level was higher in the CMHCT116 -Mφgroup . After co- culture with T lymphocytes , the cell survival rate are the most in CMHCT116 -Mφgroup , while the levels of TNF-αand IFN-γwere the lowest. After the addition of Ken , the polarization ratio and markers of M2 macrophages decreased . Compared with CMHCT116 -Mφ group , the expression of PD-L1 in HCT116 cells of the CM (HCT116 + Ken) -Mφ group de- creased . Conclusion Highly metastatic colorectal cancer cells induce polarization of M2 macrophages by secreting KLF4 , promote PD-L1 expression in colorectal cancer cells , facilitate tumor immune escape , and provide potential targets for clinical immunotherapy .