乳酸脱氢酶与肿瘤免疫代谢研究进展

周文丽; 缪明永

doi:10.16689/j.cnki.cn11-9349/r.2020.04.004

肿瘤代谢与营养电子杂志 >

2020 , Vol. 7 >Issue 4: 396 - 401

DOI: https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.04.004

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乳酸脱氢酶与肿瘤免疫代谢研究进展

周文丽 ,
缪明永

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1.海军军医大学附属长征医院肿瘤科，上海 200070；2.海军军医大学基础医学院生物化学与分子生物学教研室，上海 200433

网络出版日期: 2021-04-12

基金资助

国家自然科学基金项目（81672888）

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Research progress on lactatedehydrogenase and immunometabolism in cancer

Zhou Wenli ,
Miao Mingyong

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1.Department of Medical Oncology, Changzheng Hospital, Navy Medical University, Shanghai 200070, China；2.Department of Biochemistry and Molecular Biology, Navy Medical University, Shanghai 200433, China

Online published: 2021-04-12

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摘要

不同免疫细胞亚群的代谢特征有所不同，抗肿瘤免疫细胞主要以有氧酵解和谷氨酰胺分解代谢提供代谢的物质与能量，而促进肿瘤发生和进展的抑制性免疫细胞亚群可利用肿瘤细胞代谢产物通过脂肪酸代谢等途径获取能量及中间产物。乳酸作为糖酵解途径的重要产物，直接或间接地影响肿瘤生物学行为，参与肿瘤免疫微环境调控。乳酸代谢的关键酶乳酸脱氢酶（LDH）常在肿瘤组织中高表达，是肿瘤微环境中连接各种免疫细胞代谢的关键酶之一，可激活某些信号传导途径和调控免疫应答参与肿瘤发生、发展。LDH水平升高主要由于肿瘤糖酵解活性增加和肿瘤缺氧坏死引起，其为免疫抑制性微环境的重要驱动者，LDH水平在一定程度上反映并可用于肿瘤糖酵解活性和免疫代谢状态的评估。本文对LDH与T淋巴细胞、巨噬细胞、树突状细胞等免疫细胞的代谢相关研究进行综述，旨在探究其在恶性肿瘤预后评估、抗肿瘤治疗尤其是免疫治疗疗效预测及监测中的可能应用。

关键词： 乳酸脱氢酶; 糖酵解; 肿瘤免疫代谢; 免疫治疗; 疗效预测

本文引用格式

周文丽 , 缪明永 . 乳酸脱氢酶与肿瘤免疫代谢研究进展[J]. 肿瘤代谢与营养电子杂志, 2020 , 7(4) : 396 -401 . DOI: 10.16689/j.cnki.cn11-9349/r.2020.04.004

Abstract

The metabolic characteristics are different in different immune cell subsets. The immune cells in antitumor adaptive immunity mainly rely on aerobic glycolysis and glutamine catabolism to obtain energy and metabolites. Immunosuppressive cells in promoting cancer occurrence and progression can use the metabolites from cancer cells to get energy and intermediate products through fatty acid metabolism or other manners. As the critical product of glycolysis, lactic acid directly or indirectly affects the biological behavior of cancer and immunometabolism in tumor microenvironment. Lactate dehydrogenase （LDH） is a key enzyme connecting the metabolism of immune cells by lactic acid metabolism, generally with high expression in cancers, which regulates immune response and participates in carcinogenesis and development by activating some signal transduction pathway. It is identified as an important driver of immunosuppressive microenvironment. The increase of LDH level is mainly caused by the increase of glycolysis activity and hypoxia necrosis in cancer. To some extent, the levels of LDH can reflect and be used for the assessment of glycolysis activity and immune metabolism. However, the roles of LDH in immunometabolic regulation varies in different immune cells such as T lymphocytes, macrophages and dendritic cells. This paper reviews the researches on LDH and metabolism of these immune cells to explore the possible application in evaluating prognosis, predicting and monitoring efficacy of anti-tumor treatment, especially in cancer immunotherapy.

Key words： Lactate dehydrogenase; Glycolysis; Tumor immune metabolism; Immunotherapy; Efficacy prediction

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