Evidence map›Paper›PMID 28319047›Full record

ArticleThe Journal of clinical investigation2017

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas.

Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 299 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
299citing papers in PubMed, 1 pooled it
21.4field-weighted citation impact, top 1% of its field
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

299 citing papers in PubMed, 1 synthesis or guideline pooled it, 402 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  5. Article
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  7. Article
  8. Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  9. Article
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  11. Article
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  14. IDH1 Mutant Glioma Favors Group 3 Innate Lymphoid Cells and Is Resistant to Immune Checkpoint Expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. Article
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  20. Review

239 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 2 countries.

Gary Kohanbash
Diego A Carrera
Shruti Shrivastav
Brian J Ahn
Naznin Jahan
Tali Mazor
Zinal S Chheda
Kira M Downey
Payal B Watchmaker
Casey Beppler
Rolf Warta
Nduka A Amankulor
Christel Herold-Mende
Joseph F Costello
Hideho Okada
UCSF Helen Diller Family Comprehensive Cancer Center · USHeidelberg University · DEUniversity of Pittsburgh · USParker Institute for Cancer Immunotherapy · USUniversity of California, San Francisco · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
PREDOCTORAL TRAINING IN BIOMEDICAL SCIENCEST32GM008568 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANSEL, KARL MARK · 1995 to 2019
$6.3M
Imaging Guided Genomics of Malignant TransformationR01CA169316 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2013 to 2017
$3.0M
Novel Immunotherapy of Glioma using miR-17-92 Transfected T CellsR01NS055140 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OKADA, HIDEHO · 2007 to 2015
$2.6M
Novel adoptive transfer therapy for glioma using CAR-transduced Type17 T-cellsR21NS083171 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2014 to 2015
$791k
Antigens for Molecularly Targeted Vaccines for Progressive GliomaR21NS093654 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F, OKADA, HIDEHO · 2015 to 2016
$436k
NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA169316NCI NIH HHS T32 CA151022NIGMS NIH HHS T32 GM008568NINDS NIH HHS R01 NS055140NINDS NIH HHS R21 NS083171NINDS NIH HHS R21 NS093654
6 · The paper itself

Abstract

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 α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors. Given these findings, we have investigated the impact of IDH mutations on the immunological milieu in LGG. In immortalized normal human astrocytes (NHAs) and syngeneic mouse glioma models, the introduction of mutant IDH1 or treatment with 2HG reduced levels of CXCL10, which was associated with decreased production of STAT1, a regulator of CXCL10. Expression of mutant IDH1 also suppressed the accumulation of T cells in tumor sites. Reductions in CXCL10 and T cell accumulation were reversed by IDH-C35, a specific inhibitor of mutant IDH1. Furthermore, IDH-C35 enhanced the efficacy of vaccine immunotherapy in mice bearing IDH-MUT gliomas. Our findings demonstrate a mechanism of immune evasion in IDH-MUT gliomas and suggest that specific inhibitors of mutant IDH may improve the efficacy of immunotherapy in patients with IDH-MUT gliomas.

Indexed as

AnimalsBrain NeoplasmsCancer VaccinesCD8-Positive T-LymphocytesCell Line, TumorChemokinesChemotaxisGliomaHumansIsocitrate DehydrogenaseLymphocytes, Tumor-InfiltratingMice, Inbred C57BLNeoplasm TransplantationSTAT1 Transcription FactorT-Lymphocytes, CytotoxicVaccinationCancer VaccinesChemokinesIDH1 protein, humanIsocitrate DehydrogenaseSTAT1 protein, humanSTAT1 Transcription Factor

Identifiers

PMID28319047
PMCPMC5373859
OpenAlexW2596261790

What OpenQuestion holds

Textmetadata
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.