文献报告，细胞外游离的PD-L1分为可溶型PD-L1和外泌体型PD-L1（Exosomal PD-L1），Exosome携带的免疫抑制分子能发挥更强的抑制作用，但肿瘤细胞能否分泌Exosomal PD-L1及其免疫抑制作用尚无报告。我们原创性研究证实，胃癌患者血浆中存在Exosomal PD-L1，并与预后不良有关；胃癌细胞培养上清也存在Exosomal PD-L1，且能更强烈地诱导T细胞凋亡；泛素连接酶Cbl-b可通过抑制STAT5a减少Exosomal PD-L1的生成。生物信息学预测及我们的实验证实，Cbl-b是miR-1183的靶基因。本项目旨在通过细胞实验及临床标本检测证实miR-1183抑制Cbl-b，上调STAT5a及PD-L1的表达，促进Exosomal PD-L1的生成及诱导T细胞凋亡。结果将为明确Exosomal PD-L1的生成机制，克服免疫耐受提供依据。

Studies have shown that extracellular PD-L1 can be divided into soluble PD-L1 and Exosomal PD-L1. Exosomes carrying immune inhibitory molecules has stronger immunosuppressive effect in microenvironment. However, whether tumor-derived Exosomal PD-L1 is existed and its role is unclear. Our original data demonstrated that: Exosomal PD-L1 was detected in plasma of patients with gastric cancer and was related to poor prognosis; Exosomal PD-L1 has also been detected in gastric cancer cell culture supernatant, and induced stronger T cell apoptosis; Ubiquitin ligase Cbl-b suppressed production of Exosomal PD-L1 through inhibiting expression of STAT5a; Bioinformatic predictions and our experiments showed that Cbl-b was the target gene of miR-1183. In the present study, we aim to explore that miR-1183 upregulated STAT5a and PD-L1 through inhibiting Cbl-b，and then promoted the production of Exosomal PD-L1 and induced T cell apoptosis. The result of the study will be helpful in understanding the mechanism of Exosomal PD-L1 production and overcoming immune tolerance.