Evidence map›Paper›PMID 37398299›Full record

ArticlebioRxiv : the preprint server for biology2025

H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric Gliomas.

Maria B Garcia-Fabiani, Santiago Haase, Kaushik Banerjee, Ziwen Zhu, Brandon L McClellan, Anzar A Mujeeb, Yingxiang Li, Claire E Tronrud, Maria L Varela, Molly E J West and 34 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. 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

44 authors at 7 institutions in 5 countries.

Maria B Garcia-FabianiDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Santiago HaaseDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-5964-0748
Kaushik BanerjeeDepartment 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.ORCID 0000-0002-6681-9153
Brandon L McClellanDepartment 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.
Yingxiang LiDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Claire E TronrudDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maria L VarelaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Molly E J WestDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jin YuRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Padma KadiyalaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ayman W TaherDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Felipe J NúñezDepartment 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.
Andrea CombaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-3398-5753
Flor M MendezDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alejandro J Nicola CandiaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brittany SalazarDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Fernando M NunezDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Marta B EdwardsDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Rodrigo T CartaxoDepartment of Pediatrics, Chad Carr Pediatric Brain Tumor Center, University of Michigan Medical School, MI 48109, USA.
Michael NiculceaDepartment of Pediatrics, Chad Carr Pediatric Brain Tumor Center, University of Michigan Medical School, MI 48109, USA.
Carl KoschmannDepartment of Pediatrics, Chad Carr Pediatric Brain Tumor Center, University of Michigan Medical School, MI 48109, USA.
Sriram VennetiDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Montserrat Puigdelloses VallcorbaDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Emon NasajpourDepartment of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.
Giulia PericoliDepartment of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.
Maria VinciDepartment of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.
James P ChandlerDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Adam M SonabendDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID 0000-0002-8347-1945
Michael DeCuypereDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Dolores HambardzumyanDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Laura M ProloDepartment of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.ORCID 0000-0001-7737-8675
Kelly B MahaneyDepartment of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.
Gerald A GrantDepartment of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.
Claudia K PetritschDepartment of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.
Joshua D WelchDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, 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.ORCID 0000-0003-2237-2756
University of Michigan · USStanford University · USNorthwestern University · USIcahn School of Medicine at Mount Sinai · USMcGill University · CABambino Gesù Children's Hospital · ITDuke University · US

Funding

STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBMP50CA221747 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Atique U. Ahmed · 2018 to 2026
$21.4M
Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
TOOLKIT CoreU54CA261717 · NCI · STANFORD UNIVERSITY · PI Melanie Hayden Gephart · 2021 to 2026
$8.9M
Leveraging doxorubicin immune-modulation, blood-brain barrier opening, and personalized medicine for effective immunotherapy in glioblastoma. A mechanistic approach and pharmacokinetic trial.U19CA264338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adam M Sonabend · 2021 to 2026
$5.8M
Oligodendrocyte-focused rAAV gene therapy strategies for Canavan disease and LeukodystrophiesR01NS076991 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Guangping Gao · 2012 to 2026
$5.7M
Immune-suppressive Myeloid Cells in the Glioma Microenvironment: Signaling Mechanisms and Novel Therapeutic StrategiesR37NS094804 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2015 to 2021
$2.9M
Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics (Supplement)R01NS124167 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, JOERG LAHANN · 2022 to 2026
$2.6M
Novel nano-vaccine technology for inducing immunity against gliomasR01NS122536 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G, MOON, JAMES J. · 2021 to 2025
$2.6M
Uncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma.R01NS122165 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro · 2022 to 2026
$2.5M
The Role of Collagen and its Signaling Mechanisms in Glioma Progression and Invasion.R01NS122234 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pedro R. Lowenstein · 2022 to 2026
$2.4M
Identifying intercellular circuits driving cell phenotypes within a nicheR01CA243916 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JERUSS, JACQUELINE SARA, SHEA, LONNIE D · 2019 to 2023
$2.3M
Neuroimmunology of Malignant Brain Tumors: Innate MechanismsR01NS096756 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2016 to 2020
$2.1M
NCI NIH HHS P50 CA221747NCI NIH HHS R01 CA243916NCI NIH HHS U19 CA264338NCI NIH HHS U54 CA261717NIEHS NIH HHS P30 ES017885NINDS NIH HHS R01 NS076991NINDS NIH HHS R01 NS082311NINDS NIH HHS R01 NS096756NINDS NIH HHS R01 NS105556NINDS NIH HHS R01 NS110703NINDS NIH HHS R01 NS122165NINDS NIH HHS R01 NS122234NINDS NIH HHS R01 NS122536NINDS NIH HHS R01 NS124167NINDS NIH HHS R21 NS123879NINDS NIH HHS R37 NS094804
6 · The paper itself

Abstract

Diffuse hemispheric glioma (DHG), H3 G34-mutant, representing 9-15% of cases, are aggressive Central Nervous System (CNS) tumors with poor prognosis. This study examines the role of epigenetic reprogramming of the immune microenvironment and the response to immune-mediated therapies in G34-mutant DHG. To this end, we utilized human G34-mutant DHG biopsies, primary G34-mutant DHG cultures, and genetically engineered G34-mutant mouse models (GEMMs). Our findings show that the G34 mutation alters histone marks' deposition at promoter and enhancer regions, leading to the activation of the JAK/STAT pathway, which in turn results in an immune-permissive tumor microenvironment. The implementation of Ad-TK/Ad-Flt3L immunostimulatory gene therapy significantly improved median survival, and lead to over 50% long term survivors. Upon tumor rechallenge in the contralateral hemisphere without any additional treatment, the long-term survivors exhibited robust anti-tumor immunity and immunological memory. These results indicate that immune-mediated therapies hold significant potential for clinical translation in treating patients harboring H3.3-G34 mutant DHGs, offering a promising strategy for improving outcomes in this challenging cancer subtype affecting adolescents and young adults (AYA). STATEMENT OF SIGNIFICANCE: This study uncovers the role of the H3.3-G34 mutation in reprogramming the tumor immune microenvironment in diffuse hemispheric gliomas. Our findings support the implementation of precision medicine informed immunotherapies, aiming at improving enhanced therapeutic outcomes in adolescents and young adults harboring H3.3-G34 mutant DHGs.

Identifiers

PMID37398299
PMCPMC10312611
OpenAlexW4380624299

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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.