CCL2通过抑制CD8+T细胞活性促进NSCLC肿瘤生长  

CCL2 promotes NSCLC tumor growth by inhibiting CD8^(+)T cell activity

作　　者：徐翼 纪沛君 刘兴元 李杰 刘治利 XU Yi;JI Peijun;LIU Xingyuan;LI Jie;LIU Zhili(Department of Cardiothoracic Surgery,Jiangjin Central Hospital,Chongqing 402260,China)

机构地区：[1]重庆市江津区中心医院胸心外科,402260

出　　处：《免疫学杂志》2022年第7期597-604,共8页Immunological Journal

摘　　要：目的探讨非小细胞肺癌(NSCLC)源性单核细胞趋化蛋白-1(MCP-1/CCL2)诱导的T细胞在肿瘤免疫微环境中的作用和相关机制。方法通过q RT-PCR实验检测NSCLC组织和癌旁组织中T细胞亚群标志物和CCL2的表达水平,分析检测CCL2与肿瘤组织中T细胞亚群浸润的相关性;CCK8检测CCL2敲低或者过表达对NSCLC细胞增殖能力的影响;构建C57小鼠和SCID小鼠荷瘤模型,观察CCL2表达变化对小鼠肿瘤生长情况的影响,并通过流式细胞术检测肿瘤中T细胞亚群的变化;共培养表达CCL2的LLC细胞与CD8+T细胞,检测T细胞活性的变化。利用CCL2抑制剂处理LLC荷瘤的C57小鼠和SCID小鼠,观察其对小鼠肿瘤生长的作用。结果与癌旁正常组织相比,NSCLC组织中CCL2表达水平显著升高;NSCLC组织中CD8+、CD4+、CD25、Foxp3+与癌旁正常组织相比无显著差异;NSCLC组织中CCL2表达与T细胞浸润无显著相关性;敲低或者过表达CCL2对于NSCLC细胞的增殖能力无显著影响;CCL2过表达可以促进C57小鼠的成瘤能力,但是对SCID小鼠的成瘤能力无显著影响;CCL2可以抑制CD8+T细胞的活性;CCL2抑制剂能够抑制C57小鼠的成瘤能力,但是对SCID小鼠的成瘤能力没有影响。结论CCL2通过抑制CD8+T细胞的活性诱导抑制性肿瘤免疫微环境形成,最终促进NSCLC的发生发展。To investigate the role of T cells induced by monocyte chemoattractant protein-1(MCP-1/CCL2derived from non-small cell lung cancer(NSCLC)in tumor immune microenvironment,the expression levels of T cell subsets markers and CCL2 in NSCLC and adjacent tissues were detected by qRT PCR,and the correlation between CCL2 and T cell subsets infiltration in tumor tissues was analyzed.CCK8 was used to detect the effect of CCL2 knockdown or overexpression on the proliferation of NSCLC cells.The tumor bearing models of C57 mice and SCID mice were constructed to observe the effect of CCL2 expression on tumor growth,and the changes of T cell subsets in tumors were detected by flow cytometry;LLC cells expressing CCL2 and CD8^(+)T cells were co cultured to detect the changes of T cell activity.CCL2 inhibitor was used to treat LLC tumor bearing C57 mice and SCID mice,and its effect on tumor growth was observed.Data showed that the expression level of CCL2 in NSCLC was significantly higher than that in adjacent normal tissues;there was no significant difference in CD8+,CD4+,CD25and Foxp3+between NSCLC and adjacent normal tissues;there was no significant correlation between CCL2expression and T cell infiltration in NSCLC;and knockdown or overexpression of CCL2 had no significant effect on the proliferation of NSCLC cells.CCL2 overexpression can promote the tumorigenicity of C57 mice,but it has no significant effect on the tumorigenicity of SCID mice.CCL2 can inhibit the activity of CD8+T cells;CCL2 inhibitor could inhibit the tumorigenicity of C57 mice,but had no effect on the tumorigenicity of SCID mice.In a word,CCL2induces the formation of inhibitory tumor immune microenvironment by inhibiting the activity of CD8^(+)T cells,and finally promotes the occurrence and development of NSCLC.

关 键 词：非小细胞肺癌 单核细胞趋化蛋白-1 T淋巴细胞 免疫微环境 

分 类 号：R734.2[医药卫生—肿瘤]