Liu Hui, Pan Mengmeng, Liu Mengxia, Zeng Lin, Li Yumeng, Huang Zhen, Guo Chunlei, Wang Hui
Henan Key Laboratory of Immunology and Targeted Drug, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan, China.
Front Immunol. 2024 Nov 26;15:1496390. doi: 10.3389/fimmu.2024.1496390. eCollection 2024.
Lactate has been traditionally regarded as a mere byproduct of glycolysis or metabolic waste. However, an increasing body of literature suggests its critical role in regulating various physiological and pathological processes. Lactate is generally associated with hypoxia, inflammation, viral infections, and tumors. It performs complex physiological roles by activating monocarboxylate transporter (MCT) or the G protein-coupled receptor GPR81 across the cell membrane. Lactate exerts immunosuppressive effects by regulating the functions of various immune cells (such as natural killer cells, T cells, dendritic cells, and monocytes) and its role in macrophage polarization and myeloid-derived suppressor cell (MDSC) differentiation in the tumor microenvironment. Lactic acid has also recently been found to increase the density of CD8 T cells, thereby enhancing the antitumor immune response. Acute or chronic inflammatory diseases have opposite immune states in the inflammatory disease microenvironment. Factors such as cell types, transcriptional regulators, ionic mediators, and the microenvironment all contribute to the diverse functions lactate exhibits. Herein, we reviewed the pleiotropic effects of lactate on the regulation of various functions of immune cells in the tumor microenvironment and under inflammatory conditions, which may help to provide new insights and potential targets for the diagnosis and treatment of inflammatory diseases and malignancies.
乳酸传统上仅被视为糖酵解的副产物或代谢废物。然而，越来越多的文献表明其在调节各种生理和病理过程中起着关键作用。乳酸通常与缺氧、炎症、病毒感染和肿瘤相关。它通过激活细胞膜上的单羧酸转运体（MCT）或G蛋白偶联受体GPR81发挥复杂的生理作用。乳酸通过调节各种免疫细胞（如自然杀伤细胞、T细胞、树突状细胞和单核细胞）的功能发挥免疫抑制作用，以及其在肿瘤微环境中巨噬细胞极化和髓源性抑制细胞（MDSC）分化中的作用。最近还发现乳酸会增加CD8 T细胞的密度，从而增强抗肿瘤免疫反应。急性或慢性炎症性疾病在炎症性疾病微环境中具有相反的免疫状态。细胞类型、转录调节因子、离子介质和微环境等因素都导致了乳酸所表现出的多种功能。在此，我们综述了乳酸在肿瘤微环境和炎症条件下对免疫细胞各种功能调节的多效性作用，这可能有助于为炎症性疾病和恶性肿瘤的诊断和治疗提供新的见解和潜在靶点。
