tRNA来源小RNA（tsRNAs，18-40nt）是一类新型非编码小RNA，被报道参与调控多种生理病理活动。研究发现tsRNAs同样在外泌体中富集，但关于外泌体内tsRNAs是否具有特定的生物学功能尚未见报道。肿瘤相关巨噬细胞（TAMs）作为肿瘤微环境的重要组分，其极化状态直接影响肿瘤免疫逃逸的发生，但对于肝癌(HCC)如何影响TAMs极化的机制尚未阐明。我们前期研究发现，在HCC病人血浆外泌体中tsRNAs显著富集且与正常人差异显著；进一步发现HCC分泌的外泌体可携带tsRNAs进入巨噬细胞并调控其极化过程。基于此，本项目以外泌体tsRNAs为主线，以HCC免疫逃逸为切入点，系统研究HCC外泌体tsRNA调控TAMs极化促进肿瘤免疫逃逸的分子机制。本项目将揭示外泌体tsRNA作为信号分子介导细胞间通讯交流的新生物学功能，对阐明肝癌免疫逃逸的发生机制和研制新的靶标药物具有重要意义。

tRNA-derived small RNAs (tsRNAs), usually 18~40 nucleotides (nt) in length, are novel small non-coding RNAs that have been reported to involve in various biological processes. Recent studies have found that tsRNAs are enriched in exosomes, but little is known about whether exosomal tsRNAs has special biological functions. As main component of tumor immune microenvironment, the polarization state of tumour-associated macrophages (TAMs) directly regulate immune escape of tumor. However, the fundamental questions regarding the potential mechanisms responsible for the TAMs polarization induced by hepatocellular carcinoma (HCC) remain to be elucidated. Our newly studies found that tsRNAs were significantly upregulated in exosome of HCC patient's plasma compare to normal people, and exosomes secreted by HCC cells could carry specific tsRNA into macrophages to regulate their polarization. In this project, we will investigate the function and mechanism of HCC-derived exosomal tsRNAs in regulating TAMs polarization and promoting tumor immune escape. Overall, our project may provide important information for understanding the new biological function of exosomal tsRNA as a signal molecule to mediate intercellular communication. A better understanding of the mechanism of tumor immune escape will likely provide insight to develop effective treatment targets of liver cancer.