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The oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function

ABSTRACT: The oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function

PROVIDER: PRJNA862361 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20648612_1.fastq.gz	Fastqsanger.gz
	SRR20648612_2.fastq.gz	Fastqsanger.gz
	SRR20648613_1.fastq.gz	Fastqsanger.gz
	SRR20648613_2.fastq.gz	Fastqsanger.gz
	SRR20648614_1.fastq.gz	Fastqsanger.gz

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The oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function

Project description:The tumor-derived oncometabolite D-2HG impairs CD8+ T cell function through a novel metabolic target

2022-09-01 | GSE209757 | GEO

Oncometabolite d-2HG alters T cell metabolism to impair CD8<sup>+</sup> T cell function.

Project description: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.

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Gene expression changes in hiPS-derived cardiomyocytes under R-2HG exposure and doxorubicin treatment

Project description:RNA sequencing and immunostaining in hiPS-derived cardiomyocytes indicated that the oncometabolite R-2HG exacerbated doxorubicin mediated cardiotoxicity.

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Transcriptome of human endothelial cells treated with R-2HG or S-2HG

Project description:Transcriptome profiling of human umbilical vein endothelial cells (HUVECs) treated with R-2HG or S-2HG to identify isomer-specific gene regulation.

2021-01-05 | GSE128633 | GEO

Suppression of antitumor immunity by the oncometabolite 2-hydroxyglutarate

Project description:Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment. We investigated the effects of exogenous R-2-HG on primary human T cells.

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Gene expression profile of HCT116 and HT29 cells treated with D/L2HG

Project description:The oncometabolite, 2-hydroxyglutarate (2HG), has been directly implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. To elucidate the molecular mechanisms through which 2HG contributes to cancer progression, we performed transcriptome analysis in 2HG-treated colorectal cancer HCT116 and HT29 cells.

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The anti-leukemic effect of R-2HG depends on its acting as an m6A mRNA modifier-RNA Seq-PBS / R-2HG treatment

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RNA-seq analysis after MIR4435-2HG knockdown in HemECs

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2023-10-29 | GSE236203 | GEO

The effect of 2HG level on transcriptome at different stages of male mouse meiosis

Project description:We found that L2-hydroxyglutarate (2HG) level is 15 times higher in pachytene-diplotene (PD) stage as compared to leptotene-zygotene (LZ) stage. Since 2HG shows epigenetic effects we asked if the addition of 2HG to LZ cells or the decrease of 2HG level in PD cells will cause changes in gene expression.

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Transcriptome of human endothelial cells treated with R-2HG or S-2HG

Project description:Transcriptome of human endothelial cells treated with R-2HG or S-2HG

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