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肝细胞癌免疫治疗中乳酸代谢异常及乳酸修饰的研究进展

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma.

作者信息

Xu Yiwei, Hao Xiaodong, Ren Yidan, Xu Qinchen, Liu Xiaoyan, Song Shuliang, Wang Yunshan

机构信息

Marine College, Shandong University, Weihai, China.

Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

出版信息

Front Oncol. 2023 Jan 6;12:1063423. doi: 10.3389/fonc.2022.1063423. eCollection 2022.

Abstract

Tumors meet their energy, biosynthesis, and redox demands through metabolic reprogramming. This metabolic abnormality results in elevated levels of metabolites, particularly lactate, in the tumor microenvironment. Immune cell reprogramming and cellular plasticity mediated by lactate and lactylation increase immunosuppression in the tumor microenvironment and are emerging as key factors in regulating tumor development, metastasis, and the effectiveness of immunotherapies such as immune checkpoint inhibitors. Reprogramming of glucose metabolism and the "Warburg effect" in hepatocellular carcinoma (HCC) lead to the massive production and accumulation of lactate, so lactate modification in tumor tissue is likely to be abnormal as well. This article reviews the immune regulation of abnormal lactate metabolism and lactate modification in hepatocellular carcinoma and the therapeutic strategy of targeting lactate-immunotherapy, which will help to better guide the medication and treatment of patients with hepatocellular carcinoma.

摘要

肿瘤通过代谢重编程来满足其能量、生物合成和氧化还原需求。这种代谢异常导致肿瘤微环境中代谢物水平升高,尤其是乳酸。由乳酸和乳酸化介导的免疫细胞重编程和细胞可塑性增加了肿瘤微环境中的免疫抑制作用,并正成为调节肿瘤发展、转移以及免疫检查点抑制剂等免疫疗法疗效的关键因素。肝细胞癌(HCC)中葡萄糖代谢的重编程和“瓦伯格效应”导致乳酸的大量产生和积累,因此肿瘤组织中的乳酸修饰也可能异常。本文综述了肝细胞癌中异常乳酸代谢和乳酸修饰的免疫调节以及靶向乳酸免疫治疗的策略,这将有助于更好地指导肝细胞癌患者的用药和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb62/9853001/bfd7385ac6de/fonc-12-1063423-g001.jpg

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