肝癌早期诊断困难、预后差、发病机制不明。免疫逃逸是肿瘤进展的重要过程，但肝癌作用于免疫系统的分子机制远未阐明。外泌体作为一类重要的信息载体，目前研究主要集中于其包裹的内含物如miRNA等对免疫逃逸的调控作用，而关于外泌体表面蛋白参与肝癌免疫逃逸的现象尚未见相关报道。我们前期研究发现，肝癌来源的外泌体表面特异性高表达磷脂酰丝氨酸（PS）蛋白，且血清中PS阳性外泌体可有效区分肝癌患者与正常人；体外实验显示外泌体表面PS蛋白可与CD8+T细胞表面TIM3受体结合进而抑制CD8+T细胞的功能。基于此，本项目以肝癌的免疫逃逸为主线，以PS阳性外泌体为切入点，拟通过临床样本、细胞及动物实验，鉴定分析PS阳性外泌体对肝癌诊断的价值，探究肝癌来源的外泌体表面PS蛋白通过结合CD8+T细胞TIM3受体介导其免疫逃逸的分子机制。本项目将揭示肝癌免疫逃逸新机制，对阐释肝癌的发病机理和研制新的靶标药物有重要意义。

Liver cancer is difficult in early diagnosis and has a poor prognosis and unclear pathogenesis. Immune evasion is an important process in tumor progression, but the mechanism by which liver cancer affects the immune system is unclear. As an important information carrier, the studies about exosome mainly focus on its contained inclusions, such as miRNA, on immune evasion, while few studies have reported about the involvement of exosome surface proteins in liver cancer immune evasion. Our previous studies found that liver cancer-secreted exosomes show high PS levels, and PS-positive exosomes can effectively distinguish liver cancer patients from normal controls. Morever, exosomal PS contributes to CD8+ T cell dysfunction by binding to CD8+ T cell receptor TIM3. Based on these results, this project takes liver cancer immune evasion as the main line and PS-positive exosomes as the pointcut, we will adopt clinical samples, cell lines and mouse models to explore the clinical diagnostic value of PS-positive exosomes and the mechanism of exosomal PS in regulating liver cancer immune evasion by binding to TIM3 receptor. This study will unveil the new mechanism of liver cancer immune evasion, which is of great significance for elucidating the liver cancer pathogenesis and developing new target drugs.