Evidence map›Paper›PMID 42170677›Full record

ArticleMolecular therapy. Oncology2026

Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy.

Brandon L McClellan, Jorge A Peña Agudelo, Anzar A Mujeeb, Ali A Dabaja, Ziwen Zhu, Sadhakshi Raghuram, Maria Luisa Varela, Claire Tronrud, Kaushik Banerjee, Abraham Wei and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Brandon L McClellanDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jorge A Peña AgudeloDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Anzar A MujeebDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ali A DabajaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ziwen ZhuDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sadhakshi RaghuramDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maria Luisa VarelaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Claire TronrudDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kaushik BanerjeeDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Abraham WeiDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cecilia CalatroniDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Lucia H ZhangDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Lissa Cruz RomeroDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Paul OhDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Mahmoud S AlghamriDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Andrew RobbinsDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Matthew PerriconeDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Ying WangCollege of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Brian ShayCollege of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Peter SajjakulnukitDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Costas A LyssiotisDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Joshua D WelchDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Anna SchwendemanCollege of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Pedro R LowensteinDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maria G CastroDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gliomas account for ∼80% of primary malignant brain tumors. Many CNS WHO grade 2-3 and some grade 4 gliomas harbor mutant isocitrate dehydrogenase 1 (mIDH1), which causes a gain-of-function mutation (IDH1 R132H) leading to the production of 2-hydroxyglutarate (2HG). Mutant IDH1-induced 2HG, through epigenetic reprogramming elicits an immune-permissive tumor microenvironment (TME). An immunosuppressive mechanism in the glioma TME involves adenosine production via the ectoenzyme CD73. This study investigates mIDH1's influence on CD73 expression and adenosine levels. We demonstrate that mIDH1 glioma cells exhibit reduced CD73 expression, driven by DNA hypermethylation, leading to reduced adenosine levels. Since wtIDH1 gliomas have high CD73 expression, we evaluated CD73 blockade as an immunotherapy target. We show that CD73 inhibition used as monotherapy did not improve survival in wtIDH1 glioma-bearing mice. However, when combined with immune-stimulatory Ad-TK (adenoviral vectors encoding herpes simplex virus thymidine kinase) and Ad-Flt3L (adenoviral vectors encoding FMS-like tyrosine kinase 3 ligand) gene therapy, CD73 blockade significantly enhanced therapeutic efficacy and increased anti-glioma effector T cell activity. These findings reveal that CD73 inhibition used in combination with immune-stimulatory Ad-TK/Ad-Flt3L gene therapy may be an effective treatment for wtIDH1 gliomas, which could be readily translated to the clinical arena.

Indexed as

Ad-TK/Ad-Flt3LCD73gene therapygliomaimmunotherapyMT: Regular Issuemutant IDH1

Identifiers

PMID42170677
PMCPMC13188098

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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.