Evidence map›Paper›PMID 39042445›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024

Mutant IDH Modulates Suppressive Myeloid Populations in Malignant Glioma.

Eric P Grewal, Leland G K Richardson, Jing Sun, Rishab Ramapriyan, Maria Martinez-Lage, Julie J Miller, Bob S Carter, Daniel P Cahill, William T Curry, Bryan D Choi

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Eric P Grewal *Brain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-2189-7975
Leland G K Richardson *Brain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-8309-7738
Jing SunBrain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0009-0003-8718-2125
Rishab RamapriyanBrain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-2945-3236
Maria Martinez-LageDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-5859-7562
Julie J MillerDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-1288-593X
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-3586-1324
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-2552-6546
William T CurryBrain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-8036-1847
Bryan D ChoiBrain Tumor Immunotherapy Laboratory, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-5090-2470

Funding

Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
Neuroscience Resident Research ProgramR25NS065743 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CASH, SYDNEY S, WILLIAMS, ZIV · 2009 to 2023
$11.8M
Neuroscience Resident Research ProgramUE5NS065743 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SYDNEY S CASH, Ziv Williams · 2024 to 2026
$2.6M
A Shot for LifeThe Jenny FundBrian D. Silber Memorial FundMarcus Foundation (The Marcus Foundation)National Institutes of Health (NIH) K12CA090354NCI NIH HHS K12 CA090354NINDS NIH HHS R25 NS065743NINDS NIH HHS UE5 NS065743Swim Across America (SAA)
6 · The paper itself

Abstract

purposeMutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 have critical diagnostic and prognostic significance in diffuse gliomas. Neomorphic mutant IDH activity has been previously implicated in T-cell suppression; however, the effects of IDH mutations on intratumoral myeloid populations remain underexplored. In this study, we investigate the influence of IDH status on the myeloid compartment using human glioma specimens and preclinical models. EXPERIMENTAL

designWe performed RNA sequencing and quantitative immunofluorescence on newly diagnosed, treatment-naive IDH-mutant grade 4 astrocytoma and IDH-wild-type (IDH-WT) glioblastoma (GBM) specimens. We also generated a syngeneic murine model, comparing transcriptomic and cell-level changes in paired isogenic glioma lines that differ only in IDH mutational status.

resultsAmong patient samples, IDH-mutant tumors displayed an underrepresentation of suppressive myeloid transcriptional signatures, which was confirmed at the cellular level with decreased numbers of intratumoral M2-like macrophages and myeloid-derived suppressor cells. Introduction of the mutant IDH enzyme into murine glioma was sufficient to recapitulate the transcriptomic and cellular shifts observed in patient samples.

conclusionsWe provide transcriptomic and cellular evidence that mutant IDH is associated with a quantitative reduction of suppressive myeloid cells in gliomas and that introduction of the mutant enzyme is sufficient to result in corresponding cellular changes using an in vivo preclinical model. These data advance our understanding of high-grade gliomas by identifying key myeloid cell populations that are reprogrammed by mutant IDH and may be targetable through therapeutic approaches.

Indexed as

Brain NeoplasmsGliomaIsocitrate DehydrogenaseMutationMyeloid-Derived Suppressor CellsAnimalsCell Line, TumorDisease Models, AnimalGene Expression Regulation, NeoplasticHumansMiceMyeloid CellsTranscriptomeIDH1 protein, humanIDH2 protein, humanIsocitrate Dehydrogenase

Identifiers

PMID39042445
PMCPMC11426330

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.