肿瘤相关巨噬细胞来源CD14+B7-H3+外泌体在肾癌远处转移中的作用和机制

外泌体作为“信息载体”实现细胞间生物通讯，在肿瘤转移中发挥重要作用，然而其免疫学属性在肿瘤转移中的作用和机制尚不清楚。利用前期构建的外泌体检测技术，课题组发现了一群单核巨噬细胞来源CD14+B7-H3+新型外泌体，并发现其在肾癌患者外周血中呈现“特异性”表达。鉴于B7-H3、单核巨噬细胞以及外泌体在肿瘤转移中的作用，我们推测CD14+B7-H3+外泌体可通过形成“预转移龛”，影响远处器官免疫微环境，进而促进肾癌转移。为验证上述假说，在分析CD14+B7-H3+外泌体在肾癌诊断价值的基础上，本项目拟通过体内外实验研究该群外泌体对T细胞的抑制能力和分子机制，并探讨干预CD14+B7-H3+外泌体对肾癌远处转移的影响。总之，本课题在原创性发现的基础上，旨在丰富外泌体介导肾癌远处转移的理论学说，同时评估其作为肿瘤标志物的临床实用性，具有较好的创新性和运用前景。

As an “information carrier”, exosome fulfills the biocommunication between cells and plays a significant role in tumor metastasis. However, the function and mechanism of its immunological property in tumor metastasis remains unclear. With the use of exosome detecting technique established, we found a novel group of CD14+B7-H3+ exosome derivered from mononcyte/macrophage, and noticed its “specificity” expression in the peripheral blood of renal cancer patients. In consideration of the functions of B7-H3, Tumor associated macrophages and exosome in tumor metastasis, we speculate CD14+B7-H3+ exosome can affect the immune microenviroment of remote organs by forming a “pre-transferring niche”, and thus promote renal cancer metastasis. To verify the hypothesis above, based on the analysis of CD14+B7-H3+ exosome’s diagnostic value on renal cancer, this project is intended to study on the exosome’s inhibiting ability and molecular mechanism by experiments in vitro and vivo, and to estimate the influence of intervening CD14+B7-H3+ exosome on renal cancer’s remote transfer. In a word, with the basis of original discovery, this topic is aimed at enriching the theories of exosome inducing renal cancer’s metastasis as well as evaluating its clinical usability as tumor marker. Therefore, it is embodied with favorable innovativeness and application future.