《生命科学》 2024, 36(7): 887-897

CD8⁺ T细胞在肝细胞癌中的耗竭机制

荆　郭 , 詹天诚 , 宋万骞 , 袁永康 , 康　宁^* , 张　强^*

天津中医药大学，天津 301617

摘　要：

在肝细胞癌(hepatocellular carcinoma, HCC) 中，抗原的持续刺激会使CD8+ T 细胞呈现耗竭状态，具体表现为CD8+ T 细胞表面抑制性受体(inhibitory receptors, IRs) 持续性表达上调及共表达、表观遗传和转录谱发生改变，以及代谢呈现紊乱状态等，导致CD8+ T 细胞的增殖功能衰退，免疫功能逐渐丧失，进而引起CD8+ T 细胞死亡，最终使肿瘤细胞发生免疫逃逸。本文综述了目前对CD8+ T 细胞耗竭特征及机制的最新研究进展，为靶向耗竭CD8+ T 细胞的HCC 免疫治疗提供借鉴。

通讯作者：康　宁 , Email:kangndd@163.com 张　强 , Email:zhangqiang7@foxmail.com

The mechanism of CD8⁺ T cell exhaustion in hepatocellular carcinoma

JING Guo , ZHAN Tian-Cheng , SONG Wan-Qian , YUAN Yong-Kang , KANG Ning^* , ZHANG Qiang^*

Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

Abstract:

Under continuous antigen stimulation in hepatocellular carcinoma, CD8+ T cells undergo an exhausted state through various mechanisms, which is characterized by sustained upregulation and co-expression of inhibitory receptors on the surface of CD8+ T cells, as well as changes in epigenetic and transcriptional profiles, and metabolic disorders. These factors cause impaired proliferation function of CD8+ T cells, progressive loss of immune function, and ultimately CD8+ T cell death, resulting in immune escape of tumor cells. This article provides a review of the latest research progress on the occurrence, development, characteristics, and potential mechanisms of CD8+ T cell exhaustion in hepatocellular carcinoma. It aims to serve as a reference for further mechanism research and targeted treatment of CD8+ T cell exhaustion in hepatocellular carcinoma.

Communication Author：KANG Ning , Email:kangndd@163.com ZHANG Qiang , Email:zhangqiang7@foxmail.com