聚精氨酸诱导肿瘤微环境的免疫活性及逆转cetuximab耐药性的调控机制研究

项目名称： 聚精氨酸诱导肿瘤微环境的免疫活性及逆转cetuximab耐药性的调控机制研究

项目编号： No.81502686

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： 杨勇

作者单位： 中国医科大学

项目金额： 19万元

中文摘要： 我们的前期研究发现了一个新的免疫激活剂：聚精氨酸。聚精氨酸通过TLR4激活下游的免疫信号通路。体内实验发现聚精氨酸诱导的免疫响应能够抑制肿瘤的生长。进一步研究发现，在小鼠B16肿瘤模型中，聚精氨酸能够促进cetuximab诱导肿瘤微环境的免疫活性。聚精氨酸还可以提高cetuximab对肿瘤的敏感性。这些实验结果表明，聚精氨酸诱导肿瘤微环境的免疫活性可能会影响cetuximab的治疗效果。因此本课题将进一步深入研究聚精氨酸对cetuximab耐药性的影响及其调控机制。主要研究内容如下：1. 进一步证实聚精氨酸对cetuximab敏感性的影响。2. 研究聚精氨酸对cetuximab耐药性的影响。3. 明确聚精氨酸对cetuximab 耐药性的调控机制。希望通过本课题的研究，找到新的治疗方法来促进肿瘤的靶向治疗，也为将来应用于临床提供理论基础和实验依据。

中文关键词： 聚精氨酸；肿瘤微环境；免疫活性；Cetuximab耐药性；调控机制

英文摘要： Our previous work has led us to identify polyarginine as a novel agonist of the immune system, which activates the downstream immune signaling pathway through TLR4. The in vivo experiment also showed that polyarginine-induced immune response inhibits the tumor growth. We further found that polyarginine treatment enhances cetuximab-triggered immune activation of the tumor microenvironment in a subcutaneous tumor model of B16 cells. This role of polyarginine in increasing the sensitivity of cetuximab for inhibition of tumor growth was also demonstrated. Based on the above experiments, we indicated that polyarginine-induced immune activity of the tumor microenvironment may be related to the efficacy of cetuximab. So we propose this project to investigate deeply the role of polyarginine in overcoming cetuximab resistance and trying to understand its regulating mechanism. The main research contents are as follows:.Firstly, we will deeply confirm the effect of polyarginine on the efficacy of cetuximab..Secondly, we will establish two tumor models with the cetuximab resistance and investigate the effect of polyarginine on overcoming the cetuximab resistance..Finally, we will look into throughly the regulating mechanism of polyarginine on reversal of the cetuximab resistance..The project may offer a novel promising method for enhancing the targeted cancer therapy, and also provide the theoretical basis and the experimental evidence for the future clinical trial.

英文关键词： Polyarginine;Tumor microenvironment;Immune activity;Cetuximab resistance;Regulating mechanism