Author, as appears in the article.: Notarangelo G; Spinelli JB; Perez EM; Baker GJ; Kurmi K; Elia I; Stopka SA; Baquer G; Lin JR; Golby AJ; Joshi S; Baron HF; Drijvers JM; Georgiev P; Ringel AE; Zaganjor E; McBrayer SK; Sorger PK; Sharpe AH; Wucherpfennig KW; Santagata S; Agar NYR; Suvà ML; Haigis MC
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Baquer Gómez, Gerard Sergi
Keywords: Magnetic-resonance-spectroscopy phenotype mutations mitochondria ifn-gamma idh expression differentiation dehydrogenase alpha 2-hydroxyglutarate
Abstract: Gain-of-function mutations in isocitrate dehydrogenase (IDH) in human cancers result in the production of d-2-hydroxyglutarate (d-2HG), an oncometabolite that promotes tumorigenesis through epigenetic alterations. The cancer cell-intrinsic effects of d-2HG are well understood, but its tumor cell-nonautonomous roles remain poorly explored. We compared the oncometabolite d-2HG with its enantiomer, l-2HG, and found that tumor-derived d-2HG was taken up by CD8+ T cells and altered their metabolism and antitumor functions in an acute and reversible fashion. We identified the glycolytic enzyme lactate dehydrogenase (LDH) as a molecular target of d-2HG. d-2HG and inhibition of LDH drive a metabolic program and immune CD8+ T cell signature marked by decreased cytotoxicity and impaired interferon-γ signaling that was recapitulated in clinical samples from human patients with IDH1 mutant gliomas.
Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psychology Psicología Planejamento urbano e regional / demografia Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina ii Medicina i Materiais Interdisciplinar History and philosophy of science Geografía Geociências General o multidisciplinar General medicine Farmacia Ensino Engenharias iv Engenharias iii Engenharias ii Engenharias i Educação física Economia Direito Ciencias sociales Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência política e relações internacionais Biotecnología Biodiversidade Astronomia / física Antropologia / arqueologia Administração pública e de empresas, ciências contábeis e turismo
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: gerard.baquer@estudiants.urv.cat
Author identifier: 0000-0002-4433-4972
Record's date: 2023-04-01
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.science.org/doi/10.1126/science.abj5104
Papper original source: Science. 377 (6614): 1519-1529
APA: Notarangelo G; Spinelli JB; Perez EM; Baker GJ; Kurmi K; Elia I; Stopka SA; Baquer G; Lin JR; Golby AJ; Joshi S; Baron HF; Drijvers JM; Georgiev P; Ri (2022). Oncometabolite d-2HG alters T cell metabolism to impair CD8+ T cell function. Science, 377(6614), 1519-1529. DOI: 10.1126/science.abj5104
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1126/science.abj5104
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV