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.
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