2-hydroxyglutarate rides the cancer-immunity cycle.

Iosifina P Foskolou, Lukas Bunse, Jan Van den Bossche

Journal: Current opinion in biotechnology 2023;83():102976

PMID: 37515937

Free Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: 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.; Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Institute for Infection and Immunity, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.copbio.2023.102976

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MeSH Terms: Humans, Neoplasms, Glutarates, Ketoglutaric Acids, Stereoisomerism, Mutation, Tumor Microenvironment