Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Department of Surgery, Northeast International Hospital, Shenyang, 110623, China.
Cancer Lett. 2020 Feb 1;470:197-203. doi: 10.1016/j.canlet.2019.11.029. Epub 2019 Nov 26.
Mitochondria are known as essential biosynthetic, bioenergetic and signaling organelles, and play a critical role in cell differentiation, proliferation, and death. Nowadays, cancer is emergingly considered as a mitochondrial metabolic disease. Mitochondria also play an essential role in liver carcinogenesis. Liver cells are highly regenerative and require high energy. For that reason, a large number of mitochondria are present and functional in liver cells. Abnormalities in mitochondrial metabolism in human liver are known to be one of the carcinogenic factors. Interestingly, immune checkpoints regulate mitochondrial metabolic energetics of the tumor, the tumor microenvironment, as well as the tumor-specific immune response. This regulation forms a positive loop between the metabolic reprogramming of both cancer cells and immune cells. In this review, we discuss the evidence and mechanisms that mitochondria interplay with immune checkpoints to influence different steps of oncogenesis, as well as the potential of mitochondria as therapeutic targets for liver cancer therapy.
线粒体被认为是重要的生物合成、生物能量和信号细胞器，在细胞分化、增殖和死亡中发挥着关键作用。如今，癌症被认为是一种线粒体代谢疾病。线粒体在肝癌发生中也起着至关重要的作用。肝细胞具有很强的再生能力，需要大量的能量。因此，大量的线粒体存在于肝细胞中并发挥功能。已知人类肝脏中线粒体代谢异常是致癌因素之一。有趣的是，免疫检查点调节肿瘤、肿瘤微环境以及肿瘤特异性免疫反应的线粒体代谢能量。这种调节在癌细胞和免疫细胞的代谢重编程之间形成了一个正反馈环。在这篇综述中，我们讨论了线粒体与免疫检查点相互作用影响肿瘤发生的不同阶段的证据和机制，以及线粒体作为肝癌治疗的治疗靶点的潜力。
