[CXCL8 generates an immunosuppressive microenvironment in colorectal cancer through induction of M2 macrophage infiltration and inhibition of CD8⁺ T cell infiltration].

Objective To investigate the immunomodulatory effects of CXCL8 on the microenvironment in colorectal cancer (CRC). Methods Subcutaneous transplanted tumor model in BALB/c mice was established using CXCL8-overexpressing CT26, a murine CRC cell line . Tumor growth was monitored, and after three weeks of formation, the tumors were excised, and the spleens were harvested. Firstly, the tumor single-cell suspensions were prepared, and the infiltration of M2 macrophages and CD8⁺ T cells in the tumor microenvironment were detected by flow cytometry. Additionally, the spleen single-cell suspensions were prepared and CD8⁺ T cells were sorted. T cells were co-cultured with CXCL8-overexpressing CT26 cells in vitro, and the cytotoxicity assays were performed to evaluate the killing ability of T cells. Results Overexpression of CXCL8 promoted the growth of CRC transplanted tumors. Tumor overexpressing CXCL8 exhibited increased the infiltration of M2 macrophages and decreased the infiltration of CD8⁺ T cells. However, overexpression of CXCL8 in CRC cells did not affect the cytotoxicity of CD8⁺ T cells in vitro. Conclusion CXCL8-overexpressing CRC cells promoted the infiltration of M2 macrophages and inhibited CD8⁺ T cell infiltration to generate an immunosuppressive microenvironment in CRC.