放疗是一种重要的肿瘤治疗方法，临床发现，某些原发瘤放疗能够引发远端肿瘤的消减，产生辐射远端效应，但人们对其中的机理还了解得非常有限。本项目拟通过小鼠荷瘤鼠模型研究多种肿瘤照射后对转移瘤的远端效应，对肺肠骨髓等敏感组织的损伤作用，研究辐射远端效应的发生发展条件，研究其中免疫系统对肿瘤和正常组织作用的差异性；基于能够诱发显著辐射远端效应的肿瘤，利用由受辐射肿瘤细胞、免疫细胞、肿瘤或正常细胞组成的多细胞体系，研究免疫细胞在远端效应进程中的作用机制，重点研究受辐射肿瘤细胞释放的损伤相关信号分子DAMPs（包含外泌体、miRNA和功能蛋白等）在远端效应中的作用，检测分析筛选其中的关键信号因子与调控基因，并通过构建转基因或基因敲除肿瘤细胞，利用动物实验进行反馈验证，探讨靶向增强免疫细胞活性的辐射抗肿瘤效应。研究结果有望加深对辐射远端效应免疫机制的认识，为肿瘤放疗联合免疫治疗提供新的实验和理论基础。

Radiotherapy is an important strategy for tumor therapy. Clinical phenomenon showed that radiotherapy on tumor could inhibit the growth of other metastatic tumor without irradiation and hence induces abscopal effects. However, the underlying mechanism of this abscopal effect is still obscured. This project will apply a variety of tumor-bearing mice models to study the tumor radiation induced abscopal effects (RIAE) not only on the attenuation of metastatic tumor but also on the damage to radiosensitive normal organs including lung, small intestine and bone marrow, to study the occurrence and development conditions of RIAE, and to study the different roles of immune system in RIAE on metastatic tumor ad normal tissues. Based on the findings of which kind tumors are much effective in inducing abscopal responses, this project will establish a cell co-culture system containing multi-cell lines of irradiated tumor cells, immune cells, and non-irradiated tumor cells or normal radiosensitive cells to investigate the functions of immune cells on RIAE and underlying molecular mechanisms. Especially, the roles of radiation damage related signal molecules (DAMPs, including exosomes, miRNA and functional proteins) released from irradiated tumor cells in RIAE will be paid great attentions. The circulation miRNAs, protein signals, and exosomes containing miRNA and functional proteins will be detected by a series of methods including chips, mass-spectrum, RT-PCR, Western blotting and so on to know the key signals and key genetic regulators in RIAE. Furthermore, the tumor cells effective in RIAE will be reconstructed by transfecting or knocking-out these key genes and then seeded in mice to confirm their functions on RIAE in feedback. The effect of targeted enhancement of immune function on anti-tumor treatment of radiotherapy will also be explored. The results of this study are expected to deepen the understanding of the role of immune function in RIAE and will provide a new experimental and theoretical basis for radiotherapy combined with immunotherapy.