isocitrate dehydrogenase mutations suppress stat1

DOI: 10 1172/JCI90644 Corpus ID: 4848808 Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas article{Kohanbash2017IsocitrateDM title={Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas} author={Gary Kohanbash and Diego Carrera and Shruti Shrivastav and Brian J Ahn and Naznin Jahan and Tali 2020-7-29Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas Kohanbash G Carrera DA Shrivastav S Ahn BJ Jahan N Mazor T Chheda ZS Downey KM Watchmaker PB Beppler C Warta R Amankulor NA Herold-Mende C Costello JF Okada H

The distribution of immune cells within combined

Recently Gary and colleagues found that IDH1 mutations could suppress STAT1 signaling and CD8 + T cell accumulation to promote the immune evasion ability of gliomas 34 This may partly explain why the immune microenvironment of ICC was more likely to be immune suppressed than that of HCC

Requires Mn2+ or Mg2+ for activity Unlike EC 1 1 1 42 isocitrate dehydrogenase (NADP+) oxalosuccinate cannot be used as a substrate In eukaryotes isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties and a non-allosteric NADP+-linked enzyme that is found in both mitochondria and cytoplasm [7]

Among diffusely infiltrative gliomas in adults 20%–30% contain a point mutation in isocitrate dehydrogenase 1 (IDH1 mut) which increases production of D-2-hydroxyglutarate (D2HG) This is so efficient that D2HG often reaches 30 mM within IDH1 mut gliomas Yet while up to 100 M D2HG can be detected in the circulating cerebrospinal fluid of IDH1 mut glioma patients the exposure of

The mutation in isocitrate dehydrogenase results in the production of (R)-2-hydroxyglutarate (2-HG) a signature on co-metabolite of these tumors [12] 2-HG acts at the epigenetics to suppress the expression of multiple antitumor immune genes thereby creating an immune-suppressive microenvironment to allow for the progression to a high-grade

Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in a variety of myeloid malignancies and solid tumors Mutant IDH proteins acquire a neomorphic enzyme activity to produce the putative oncometabolite D-2-hydroxyglutarate which is thought to block cellular differentiation by competitively inhibiting α-ketoglutarate-dependent dioxygenases

Information on EC 1 1 1 41

Requires Mn2+ or Mg2+ for activity Unlike EC 1 1 1 42 isocitrate dehydrogenase (NADP+) oxalosuccinate cannot be used as a substrate In eukaryotes isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties and a non-allosteric NADP+-linked enzyme that is found in both mitochondria and cytoplasm [7]

The mutation in isocitrate dehydrogenase results in the production of (R)-2-hydroxyglutarate (2-HG) a signature on co-metabolite of these tumors [12] 2-HG acts at the epigenetics to suppress the expression of multiple antitumor immune genes thereby creating an immune-suppressive microenvironment to allow for the progression to a high-grade

Mutations in isocitrate dehydrogenase (IDH) or a reduced expression of L-2-hydroxyglutarate (HG)-dehydrogenase result in accumulation of D-2-HG or L-2-HG respectively in tumor tissues D-2-HG and L-2-HG have been shown to affect T-cell differentiation and activation however effects on human myeloid cells have not been investigated so far

Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG) LGG-associated IDH mutations confer gain-of-function activity by converting alpha-ketoglutarate to the oncometabolite R-2

The mutation in isocitrate dehydrogenase results in the production of (R)-2-hydroxyglutarate (2-HG) a signature on co-metabolite of these tumors [12] 2-HG acts at the epigenetics to suppress the expression of multiple antitumor immune genes thereby creating an immune-suppressive microenvironment to allow for the progression to a high-grade

Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves via dehydrogenation of isocitrate (ICT) and reduction of NADP+ Mutations in position R132 trigger cancer by enabling IDH1 to produce d-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT

2017-3-20Isocitrate dehydrogenase mutations suppress STAT1 and CD8 + T cell accumulation in gliomas Gary Kohanbash 1 Diego A Carrera 1 Shruti Shrivastav 1 Brian J Ahn 2 Naznin Jahan 1 Tali Mazor 1 Zinal S Chheda 1 Kira M Downey 1 Payal B Watchmaker 1 Casey Beppler 3 Rolf Warta 4 Nduka A Amankulor 2 Christel Herold-Mende 4 Joseph F

2017-4-3The study "Isocitrate Dehydrogenase Mutations Suppress STAT1 And CD8+ T Cell Accumulation In Gliomas " was published in the Journal of Clinical Investigation Gliomas which develop in the brain or spinal cord are non-malignant to start with and usually treatable

The distribution of immune cells within combined

Recently Gary and colleagues found that IDH1 mutations could suppress STAT1 signaling and CD8 + T cell accumulation to promote the immune evasion ability of gliomas 34 This may partly explain why the immune microenvironment of ICC was more likely to be immune suppressed than that of HCC

Kohanbash G Carrera DA Shrivastav S et al Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas J Clin Invest 2017 127:1425-37 Zhang X Rao A Sette P et al IDH mutant gliomas escape natural killer cell immune surveillance by

Isocitrate Dehydrogenase Mutations are Better Prognostic Marker than O6-methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastomas - a Retrospective Single-centre Molecular Genetics Study of Gliomas Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas 28319047 Glioma

In a study published this week in the JCI Hideho Okada's lab at UCSF investigated whether acquired mutations in the enzyme isocitrate dehydrogenase (IDH) which are common in low-grade gliomas help these tumors become resistant to immunotherapy

Isocitrate dehydrogenases (IDHs) are critical metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (αKG) NAD(P)H and CO2 IDHs epigenetically control gene expression through effects on αKG-dependent dioxygenases maintain redox balance and promote anaplerosis by providing cells with NADPH and precursor substrates for macromolecular synthesis