CXCL8通过增加M2型巨噬细胞浸润及抑制CD8^(+)T细胞浸润促进结直肠癌免疫抑制微环境的形成  

CXCL8 generates an immunosuppressive microenvironment in colorectal cancer through induction of M2 macrophage infiltration and inhibition of CD8^(+)T cell infiltration

作　　者：邵莹 兰燕 宋冰 孙嘉颖 杨涛 SHAO Ying;LAN Yan;SONG Bing;SUN Jiaying;YANG Tao(Department of Pathophysiology,Shanxi Medical University,School of Basic Medicine,Taiyuan 030001,China;Department of Biochemistry and Molecular Biology,Shanxi Medical University,School of Basic Medicine,Taiyuan 030001,China;Department of Pharmacology,Shanxi Medical University,School of Basic Medicine,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院病理生理学教研室,山西太原030001 [2]山西医科大学基础医学院生物化学与分子生物学教研室,山西太原030001 [3]山西医科大学基础医学院药理学教研室,山西太原030001

出　　处：《细胞与分子免疫学杂志》2024年第10期880-886,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：山西省科技创新人才团队专项计划(202204051002030);山西省基础研究计划(20210302124415)。

摘　　要：目的探讨CXC趋化因子配体8(CXCL8)对结直肠癌(CRC)微环境的免疫调节作用。方法使用过表达CXCL8的鼠源CRC细胞株CT26细胞建立BALB/c小鼠皮下移植瘤模型,监测肿瘤生长情况,成瘤三周后剥离肿瘤组织并取出小鼠脾脏,一方面制备肿瘤单细胞悬液,流式细胞术检测肿瘤微环境中M2型巨噬细胞及CD8^(+)T细胞的浸润情况;另一方面制备脾脏单细胞悬液,分选脾脏CD8^(+)T细胞,在体外将T细胞与过表达CXCL8的CT26细胞共培养,细胞毒性实验检测T细胞杀伤能力。结果过表达CXCL8促进小鼠CRC移植瘤生长;过表达CXCL8的CRC组织中M2型巨噬细胞浸润增加、CD8^(+)T细胞浸润减少;过表达CXCL8的小鼠CRC细胞并不影响CD8^(+)T细胞体外杀伤能力。结论CXCL8过表达CRC细胞通过增加M2型巨噬细胞浸润及抑制CD8^(+)T细胞浸润促进CRC免疫抑制微环境的形成。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.

关 键 词：CXC趋化因子配体8(CXCL8) M2型巨噬细胞 CD8^(+)T细胞 结直肠癌(CRC) 

分 类 号：R34[医药卫生—基础医学] R574.62R735.3