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Malic enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells.
Zhang, Zhenxi; Yang, Yanting; Chen, Yang; Su, Jingyu; Du, Wenjing.
Afiliación
  • Zhang Z; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
  • Yang Y; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
  • Chen Y; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
  • Su J; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
  • Du W; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. Electronic addr
Mol Cell ; 84(17): 3354-3370.e7, 2024 Sep 05.
Article en En | MEDLINE | ID: mdl-39151423
ABSTRACT
The functional integrity of CD8+ T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8+ T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8+ T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8+ T cell activation and anti-tumor immune response in vitro and in vivo. Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8+ T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8+ T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T CD8-positivos / Proteínas Quinasas Asociadas a Muerte Celular / Fumaratos Límite: Animals / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T CD8-positivos / Proteínas Quinasas Asociadas a Muerte Celular / Fumaratos Límite: Animals / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos