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

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...

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Published inFrontiers in oncology Vol. 12; p. 1063423
Main Authors Xu, Yiwei, Hao, Xiaodong, Ren, Yidan, Xu, Qinchen, Liu, Xiaoyan, Song, Shuliang, Wang, Yunshan
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 06.01.2023
Subjects
hepatocellular carcinoma
immune regulation
immunotherapy
lactate metabolism
lactylation
Oncology
lactate metabolism
lactylation
hepatocellular carcinoma
immune regulation
immunotherapy
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Summary: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.
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This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology
Reviewed by: Sweta Sikder, National Institutes of Health (NIH), United States; Amarshi Mukherjee, University of Alabama at Birmingham, United States
Edited by: Parames C. Sil, Bose Institute, India
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2022.1063423