Xia Yixue, Gao Binghong, Zhang Xue
School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai, China.
Front Oncol. 2022 Sep 23;12:993437. doi: 10.3389/fonc.2022.993437. eCollection 2022.
Most of the primary hepatocellular carcinoma (HCC) develops from Viral Hepatitis including Hepatitis B virus, Hepatitis C Virus, and Nonalcoholic Steatohepatitis. Herein, T cells play crucial roles combined with chronic inflammation and chronic viral infection. However, T cells are gradually exhausted under chronic antigenic stimulation, which leads to T cell exhaustion in the tumor microenvironment, and the exhaustion is associated with mitochondrial dysfunction in T cells. Meanwhile, mitochondria play a crucial role in altering T cells' metabolism modes to achieve desirable immunological responses, wherein mitochondria maintain quality control (MQC) and promote metabolism regulation in the microenvironment. Although immune checkpoint inhibitors have been widely used in clinical practice, there are some limitations in the therapeutic effect, thus combining immune checkpoint inhibitors with targeting mitochondrial biogenesis may enhance cellular metabolic adaptation and reverse the exhausted state. At present, several studies on mitochondrial quality control in HCC have been reported, however, there are gaps in the regulation of immune cell function by mitochondrial metabolism, particularly the modulating of T cell immune function. Hence, this review summarizes and discusses existing studies on the effects of MQC on T cell populations in liver diseases induced by HCC, it would be clued by mitochondrial quality control events.
大多数原发性肝细胞癌（HCC）由病毒性肝炎发展而来，包括乙型肝炎病毒、丙型肝炎病毒和非酒精性脂肪性肝炎。在此过程中，T细胞与慢性炎症和慢性病毒感染共同发挥关键作用。然而，T细胞在慢性抗原刺激下会逐渐耗竭，导致肿瘤微环境中的T细胞耗竭，且这种耗竭与T细胞的线粒体功能障碍有关。同时，线粒体在改变T细胞代谢模式以实现理想的免疫反应中起关键作用，其中线粒体维持质量控制（MQC）并促进微环境中的代谢调节。尽管免疫检查点抑制剂已在临床实践中广泛应用，但其治疗效果存在一些局限性，因此将免疫检查点抑制剂与靶向线粒体生物合成相结合可能会增强细胞代谢适应性并逆转耗竭状态。目前，已有多项关于HCC中线粒体质量控制的研究报道，然而，线粒体代谢对免疫细胞功能的调节，尤其是对T细胞免疫功能的调节仍存在空白。因此，本综述总结并讨论了现有关于MQC对HCC诱导的肝脏疾病中T细胞群体影响的研究，这些研究将以线粒体质量控制事件为线索。
