肿瘤细胞内化免疫细胞（如NK细胞）可形成异质性cell-in-cell（heCIC）结构，可以导致内化的免疫细胞死亡，被认为是一种免疫调控机制，但调控heCIC形成的机制尚不清楚。我们前期利用基因芯片筛选出候选基因，发现高尔基体跨膜糖蛋白73（GP73）是调控heCIC形成的关键分子，具有负向调控作用。GP73作为肝癌早期血清标志物参与了囊泡转运和RTK等信号通路调控，在肝癌生长、转移和侵袭等病理过程中发挥重要作用，因此阐明GP73调控heCIC的形成机制，对肝癌的免疫治疗具有重要意义。本研究拟使用肝癌细胞系建立的heCIC细胞模型，对GP73进行表型分析和功能验证，并运用活细胞动态成像技术、Co-IP和裸鼠荷瘤实验等体内外多种生物学方法，结合临床病理资料，深入研究GP73调控heCIC形成的分子机制和功能，探讨heCIC形成对肝癌免疫调控的贡献，为肝癌靶向免疫治疗提供新思路。

Tumor cells internalized immune cells (such as NK cells) can form a heterotypic cell-in-cell (heCIC) structure, which can lead to the death of internalized immune cells. It is considered as an immune regulatory mechanism, but the mechanism that regulates the formation of heCIC is still unclear. In the early stage, we used gene chip to screen out candidate genes and found that golgi transmembrane glycoprotein 73 (GP73) is a key molecule that regulates the formation of heCIC and has a negative regulatory effect. GP73, as a serum marker in the early stage of liver cancer, is involved in the regulation of vesicle transport, RTK and other signaling pathways, and plays an important role in the growth, metastasis and invasion of liver cancer. Therefore, it is of great significance to elucidate the mechanism of GP73 regulating the formation of heCIC for the immunotherapy of liver cancer. This study intends to use liver cancer cell line established heCIC cell model, the GP73 phenotypic analysis and functional verification, and using living cells tumor-burdened bone dynamic imaging technology, Co - IP and nude mice experiment and so on many kinds of biological methods in vivo and in vitro, combined with clinical pathological data, in-depth study of the molecular mechanism of GP73 regulation heCIC form and function, explore the heCIC's contribution to the immune regulation of liver cancer, immunotherapy for cancer of the liver targeted provide a new way of thinking.