Department of Hematopoiesis, Sanquin Research and Department of Hematology University Medical Center, University of Amsterdam, the Netherlands.
German Cancer Consortium (DKTK) Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim Germany.
Curr Opin Biotechnol. 2023 Oct;83:102976. doi: 10.1016/j.copbio.2023.102976. Epub 2023 Jul 27.
2-hydroxyglutarate (2HG) is a biproduct of the Krebs cycle, which exists in a D- and L- enantiomer and is structurally similar to α-ketoglutarate. Both 2HG enantiomers have been described to accumulate in diverse cancer and immune cells and can influence cell fate and function. While D-2HG was originally considered as an 'oncometabolite' that aberrantly builds up in certain cancers, it is becoming clear that it also physiologically accumulates in immune cells and regulates immune function. Conversely, L-2HG is considered as an 'immunometabolite' due to its induction and regulatory function in T cells, but it can also be induced in certain cancers. Here, the authors review the effects of both 2HG enantiomers on immune cells within the tumor microenvironment.
2-羟戊二酸（2HG）是三羧酸循环的副产物，有 D-和 L-两种对映异构体，结构上与α-酮戊二酸相似。两种 2HG 对映异构体都已被描述在不同的癌症和免疫细胞中积累，并能影响细胞命运和功能。虽然 D-2HG 最初被认为是一种在某些癌症中异常积累的“致癌代谢物”，但现在越来越清楚的是，它也在免疫细胞中生理性积累并调节免疫功能。相反，L-2HG 被认为是一种“免疫代谢物”，因为它在 T 细胞中诱导和调节功能，但它也可以在某些癌症中诱导产生。在这里，作者综述了两种 2HG 对映异构体在肿瘤微环境中对免疫细胞的影响。
