Autor según el artículo: 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
Departamento: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/es de la URV: Baquer Gómez, Gerard Sergi
Palabras clave: Magnetic-resonance-spectroscopy phenotype mutations mitochondria ifn-gamma idh expression differentiation dehydrogenase alpha 2-hydroxyglutarate
Resumen: 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.
Áreas temáticas: 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
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: gerard.baquer@estudiants.urv.cat gerard.baquer@estudiants.urv.cat
Identificador del autor: 0000-0002-4433-4972 0000-0002-4433-4972
Fecha de alta del registro: 2024-07-27
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.science.org/doi/10.1126/science.abj5104
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Science. 377 (6614): 1519-1529
Referencia de l'ítem segons les normes 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
DOI del artículo: 10.1126/science.abj5104
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2022
Tipo de publicación: Journal Publications
Repositori URV