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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas

ABSTRACT: Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas

PROVIDER: PRJNA922456 | ENA |

REPOSITORIES: ENA

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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [RNA-Seq]

Project description:Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [RNA-Seq]

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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [scRNA-seq]

Project description:Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [scRNA-seq]

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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [RNA-Seq]

Project description:The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression, but only a limited view of a highly complex glioma associated immune contexture across isocitrate dehydrogenase mutation (IDH) classified gliomas is known. Herein, we present an unprecedentedly comprehensive view of myeloid and lymphoid cell type diversity with our m-RNA sequencing interrogation.

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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas [scRNA-seq]

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Gene expression profile of T cells from Isocitrate Dehydrogenase (IDH) stratified human gliomas at single cell level

Project description:The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression, but only a limited view of a highly complex glioma associated immune contexture across isocitrate dehydrogenase mutation (IDH) classified gliomas is known. Herein, we present an unprecedentedly comprehensive view of T cells from brain TIME at single cell resolution, which served as part of our pan-cancer T cell atlas analysis.

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Gene expression profile of T cells from Isocitrate Dehydrogenase (IDH) stratified human gliomas at single cell level

Project description:Gene expression profile of T cells from Isocitrate Dehydrogenase (IDH) stratified human gliomas at single cell level

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Loss of retinoic acid signaling drives immune escape in IDH mutant gliomas

Project description:Gliomas are immunologically cold tumors that can be broken into several categories based on either RNA expression profiles or methylation profiles, with isocitrate dehydrogenase (IDH) mutations defining a major segregration between types. IDH mutant gliomas often exhibit defects in the retinoic acid pathway. We treated mice harboring IDH mutant gliomas with all-trans retinoic acid, and found that this treatment cause reductions in tumor growth and a swith in immune profiles in the tumor microenvironment.

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Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib

Project description:Isocitrate dehydrogenase (IDH)-mutant gliomas have distinctive metabolic and biological traits that may render them susceptible to targeted treatments. Here, by conducting a high-throughput drug screen, we pinpointed a specific susceptibility of IDH-mutant gliomas to zotiraciclib (ZTR). ZTR exhibited selective growth inhibition across multiple IDH-mutant glioma in vitro and in vivo models. Mechanistically, ZTR at low doses suppressed CDK9 and RNA Pol II phosphorylation in IDH-mutant cells, disrupting mitochondrial function and NAD+ production, causing oxidative stress.,. Integrated biochemical profiling of ZTR kinase targets and transcriptomics unveiled that ZTR-induced bioenergetic failure was linked to the suppression of PIM kinase activity. We posit that the combination of mitochondrial dysfunction and an inability to adapt to oxidative stress resulted in significant cell death upon ZTR treatment, ultimately increasing the therapeutic vulnerability of IDH-mutant gliomas. These findings prompted a clinical trial evaluating ZTR in IDH-mutant gliomas towards precision medicine (NCT05588141).

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Immune landscape of Isocitrate Dehydrogenase (IDH) stratified human gliomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-05 | GSE222522 | GEO

IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation (Related accession no. GSE275791) - Spatial transcriptomics dataset

Project description:Discovering the cell-of-origin harboring the initial driver mutation provides a fundamental basis for understanding tumor evolution and development of new treatments. For isocitrate dehydrogenase (IDH)-mutant gliomas–the most common malignant primary brain tumors in adults under 50–the cell-of-origin remains poorly understood. Here, using patient brain tissues and genome-edited mice, we identified glial progenitor cells (GPCs), including oligodendrocyte progenitor cells (OPCs), as the glioma-originating cell type harboring the IDH mutation as the initial driver mutation. We conducted comprehensive deep sequencing, including droplet digital PCR and deep panel and amplicon sequencing to 142 tissues from 70 patients (32 IDH-mutant gliomas and 38 IDH-negative controls) comprising tumors, histologically normal peritumoral regions or subventricular zones (SVZs), and blood. Surprisingly, low-level IDH mutation was found in the normal peritumor away from the tumor in 37.9% (11 of 29) of IDH-mutant glioma patients, whereas no IDH mutation was detected in the SVZ. Integrating cell-type–specific mutations analysis, the direction of clonal evolution, spatial transcriptomics from patient brains and a novel IDH-mutant glioma mouse model arising from mutant OPCs, we determined that GPCs, including OPCs, harboring the initial driver mutation are responsible for the development and evolution of IDH-mutant gliomas. In summary, our results demonstrate that GPCs containing the IDH mutation are the cells-of-origin harboring the initial driver mutation in IDH-mutant gliomas.

2026-01-13 | GSE302642 | GEO

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