雌激素受体β1在白介素6介导肺鳞癌免疫反应中的作用及机制研究

项目名称： 雌激素受体β1在白介素6介导肺鳞癌免疫反应中的作用及机制研究

项目编号： No.81501985

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 唐和孝

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 肺癌免疫治疗潜在的巨大临床收益是目前国内外研究的重点和难点，大量研究表明雌激素（E2）与肺癌最重要的免疫介质之一白细胞介素6（IL-6）具有显著的相关性，但E2主要功能受体亚型ERβ1参与IL-6介导肺癌免疫反应的作用及机制尚无报道。我们在前期研究ERβ1与IL-6基础上，结合最新预实验结果提出假说：肺鳞癌中ERβ1与IL-6表达高度相关，E2可能通过ERβ1促进肺鳞癌患者IL-6的分泌，进而促进肺鳞癌进展。本项目扩大样本检测肺鳞癌组织中ERβ1与IL-6的表达；建立稳定高或低表达ERβ1肺鳞癌细胞株，检测细胞效应和IL-6启动子活性及关键分子表达，重点探讨ERβ1在IL-6介导肺鳞癌免疫反应中的作用；通过质粒构建、慢病毒感染和皮下移植瘤建立稳定高或低表达ERβ1小鼠肺鳞癌模型验证上述结论。本项目阐明ERβ1在IL-6介导肺鳞癌免疫反应中的作用及机制，为肺鳞癌的免疫治疗寻找更为精确的靶点。

中文关键词： 肿瘤免疫；肺鳞癌；雌激素受体β1；白介素6

英文摘要： Lung cancer immunotherapy contained huge potential clinical benefit is key issues and challenges. Numerous studies have confirmed that interleukin-6 (IL-6), one of the most important immune mediators of lung cancer, shows a significant correlation with Estrogen (Estrogen, E2, the main function of the estrogen receptor subtypes in lung cancer is ERβ, and the key isoform is ERβ1). So it is possible to increase lung cancer immune effect IL-6-mediated by E2 intervention, while the underlying mechanisms are poorly understood. ERβ1 is highly correlated with IL-6 in lung squamous cell immunity, but how to participate in IL-6-mediated immune responses in lung cancer has not been reported. On the basis of pre-experiment and the long-period study on the mechanism of which ERβ1 and IL-6, we propose several hypotheses: ERβ1 is highly correlated with IL-6 in lung squamous cell carcinoma (LSCC), and E2 may promote the secretion of IL-6 in patients with LSCC through ERβ1, thus contributing to the progress of LSCC. Firstly, the project will expand the samples of LSCC to test the expression of ERβ1 and IL-6. Furthmore, we will establish a stable high or low expression of ERβ1 in LSCC cell in vitro experiments to detect proliferation, apoptosis, migration and other cell effects. At the same time, we will also detect IL-6 promoter activity and the expression of key signaling pathway molecule, to explore the different roles of ERβ1 and IL-6 in LSCC, and to explore the effect of ERβ1 in to explore IL-6-mediated immune responses. Finally, we will establish stable mouse model of LSCC which steadily expresses ERβ1 (high or low) by plasmid, viral infections, and subcutaneous xenografts, to further verify the above conclusions. This project contributes to clarify the role and mechanism of ERβ1 in IL-6-mediated immune responses of LSCC, and to find more precise targets for LSCC immunotherapy.

英文关键词： Tumor immunity;Squamous lung carcinoma ;Estrogen receptor beta isoforms 1;Interleukin-6