ILC2及Tfh的活性与肺腺癌免疫抑制状态的相关性研究

Correlation between ILC2 and Tfh activities and immunosuppressive status of lung adenocarcinoma

为探讨ILC2和滤泡辅助性T细胞(follicular helper T cell,Tfh)是否协同促进并维持肺腺癌免疫抑制状态,选择肺腺癌患者为研究对象,采用FACS检测患者外周血中ILC2和Tfh的比例;qRT-PCR检测外周血ILC2及Tfh相关因子的表达水平,并对ILC2及Tfh进行相关性分析。结果显示,与对照组比较,肺腺癌患者外周血中ILC2的比例及其相关因子IL-33、IL-25、胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)、IL-13、IL-5及IL-4 mRNA的表达水平均升高(P<0.05),CD3^(+)CD4^(+)CXC趋化因子受体5(CXC chemokine receptor 5,CXCR5)^(+)T细胞及PD-1^(+)CXCR5^(+)Tfh的比例升高(P<0.05),CD3^(+)CD4^(+)CXCR5-T细胞的比例下调(P<0.01),Tfh相关因子IL-21下调(P<0.05);ILC2与PD-1^(+)CXCR5^(+)Tfh呈正相关(r=0.390,P=0.0401)。该研究提示,ILC2的活性增强以及Tfh的活性减弱可能共同维持了肺腺癌患者的免疫抑制状态。

To explore whether ILC2 and follicular helper T cells(Tfh)cooperate to promote and maintain the immunosuppressive status of lung adenocarcinoma,the proportions of ILC2 and Tfh in peripheral circulation of lung adenocarcinoma patients were analyzed by FACS.The mRNA levels of ILC2 and Tfh-related cytokines were determined by qRT-PCR and the correlation between ILC2 and Tfh was examined.The results showed that compared to control group,both the proportions of ILC2 and the mRNA levels of ILC2 related cytokines IL-33,IL-25 were elevated in patients with lung adenocarcinoma,along with increased expression of thymic stromal lymphopoietin(TSLP),IL-13,IL-5,and IL-4 mRNA(P<0.05).The proportions of CD3^(+)CD4^(+)CXC chemokine receptor 5(CXCR5)^(+)T cells and PD-1^(+)CXCR5^(+)Tfh increased(P<0.05)whereas the proportion of CD3^(+)CD4^(+)CXCR5-T cells decreased(P<0.01).In addition,Tfh associated cytokine IL-21 was down-regulated(P<0.05).The data reveals a positive correlation between ILC2 and PD-1^(+)CXCR5^(+)Tfh(r=0.390,P=0.0401).Altogether,the results suggest that increased ILC2 activity and reduced Tfh activity may synergistically contribute to the immunosuppressive status of patients with lung adenocarcinoma.