Erb-(IL10)2介导的T细胞活化在电离辐射远隔效应中的作用及机制研究

放射远隔效应指电离辐射作用下，未照射的远处肿瘤出现病灶缩小的现象，它可能与放射激发机体抗肿瘤免疫反应有关。局部照射肿瘤引起的免疫应答不足以对远处肿瘤产生杀伤作用，联合免疫治疗可能增强放射免疫原性而达到抑制远处病灶的目的。本课题组前期在放射与偶联EGFR融合蛋白Erb-(IL10)2联合治疗的小鼠黑色素瘤模型中，观察到显著的肿瘤放射远隔效应，但其机制仍有待揭示。既往文献报道IL-10在肿瘤中能够募集CD8+ T细胞并活化，而CD8+ T细胞又是抗肿瘤免疫的重要效应细胞，由此我们提出假设：Erb-(IL10)2特异性聚集在肿瘤部位，通过介导CD8+ T细胞募集、活化，增强肿瘤免疫应答，最终诱导放射远隔效应。本项目拟证实Erb-(IL10)2促进放射远隔效应，通过筛选有显著变化的T细胞群及相关因子，探讨Erb-(IL10)2在放射远隔效应中的作用机制，为开辟放射在肿瘤治疗中的新领域提供理论基础。

Radiation abscopal effect refers to a regression in non-irradiated distant tumor lesions. It may be related to the radiation-induced anti-tumor immune response. The immune response induced by local irradiation is not enough to kill the distant tumor, while the combination therapy may enhance the immunogenicity of the tumor and inhibit the distant lesions. Our research group previously observed a significant abscopal effect induced by EGFR fusion protein Erb-(IL10)2 in melanoma model, however, its mechanism is yet to be revealed. Previous literature has reported that IL-10 could accumulate CD8+ T cells in tumor site, which play an important role in anti-tumor inmuno-response. Hence, our hypothesis is proposed: Erb-(IL10)2 specifically accumulated at the tumor site, mediated T cell activation, enhanced immune response, and eventually induced radiation abscopal effect. This project aims to prove that Erb-(IL10)2 could promote radiation remote effect, by means of screening T cell populations and related factors that had significant changes, further the study of Erb-(IL10)2 in the radiation mechanism of the abscopal effect, so as to provide a theoretical basis for a new field of radiotherapy in the treatment of tumor.