血小板介导循环肿瘤细胞（CTC）的免疫逃逸，是CTC存活及肿瘤转移形成的基础。但是，血小板介导肝癌CTC免疫逃逸的具体机制尚未明确。申请人前期在肝癌CTC的临床意义、生物学特征及检测平台等方面取得了一系列成果。近期，申请人通过对肝癌CTC单细胞测序、质谱、生信等预实验结果原创性发现：血小板通过释放外泌体，递送ITGB3/Src分子，磷酸化CTC中的CD155，提高其稳定性，从而促进免疫逃逸。我们拟采用免疫-肿瘤细胞共培养及动物模型研究血小板外泌体及其中ITGB3、Src蛋白在CTC免疫逃逸中的作用，并探索Src催化的CD155磷酸化对CD155稳定性的影响。同时，拟通过临床队列评估ITGB3+/Src+/CD155+ CTC作为肝癌预后标志物的诊断价值。本研究揭示了一种外泌体介导细胞间通讯实现CTC免疫逃逸的全新模式，并探索了“免疫逃逸表型”CTC作为一种新的标志物在肝癌预后中的临床价值。

Immune escape of circulating tumor cells (CTCs) mediated by platelets provides a breeding ground for CTCs survival and metastasis of cancer. However, the specific mechanism of platelet-mediated CTCs immune escape in hepatocellular carcinoma (HCC) has not been clarified. The applicant has obtained some achievements in her previous researches on CTCs in HCC ranging from the clinical significance and biological characteristics of CTCs to the optimization of analytical platform and assays. By preliminary experiments of single cell sequencing and mass spectrometry analysis on HCC CTCs recently, the applicant revealed that the release of exosomes containing ITGB3 and Src from platelets could phosphorylate CD155 on CTC by delivering ITGB3/Src molecules and increase the stability of CD155, eventually promote the immune escape of CTCs. This study intends to investigate the role of platelet-derived exosomes and ITGB3/Src proteins in CTCs immune escape using the immune cell-tumor cell co-culture model and animal models. The effect of CD155 phosphorylation catalyzed by Src on its stability will also be explored. Meanwhile, the clinical significance of ITGB3+/Src+/CD155+ CTCs as a diagnostic marker of HCC will be evaluated by clinical cohort analysis. This study aims to reveal a new model of exosome-mediated intercellular communication which achieved the immune escape of CTCs as well as the clinical significance of the "immune escape phenotype" CTCs as a new marker in predicting the prognosis of HCC.