Evidence map›Paper›PMID 41648606›Full record

ArticlebioRxiv : the preprint server for biology2026

MIF-mediated reprogramming of myeloid lineage within the glioma tumor microenvironment impacts the efficacy of immune stimulatory gene therapy.

Ziwen Zhu, Noah C Kanis, Anthony E George, Michael Albdewi, Yingxiang Li, Anzar A Mujeeb, Brandon L McClellan, Gurveer Singh, Jialin Liu, Wajd N Al-Holou and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Ziwen ZhuDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-6681-9153
Noah C KanisDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Anthony E GeorgeDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Michael AlbdewiDepartment 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.
Anzar A MujeebDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brandon L McClellanDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Gurveer SinghDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jialin LiuDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-9984-7695
Wajd N Al-HolouDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jason A HethDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Joshua D WelchDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-5869-2391
Justin D LathiaDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA.
Pedro R LowensteinDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Richard BucalaSection of Rheumatology, Allergy & Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Maria G CastroDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Funding

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
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
Interactions between the tumor cells and the neuro-immune microenvironment in mutant IDH1 gliomas: implications for therapeuticsR01NS105556 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2018 to 2021
$1.9M
Defining the Pathogenic Contribution of High Genotypic MIF ExpressionR01AR078334 · NIAMS · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2021 to 2025
$1.8M
Mechanisms of glioma growth and invasion novel therapeutic strategiesR01NS082311 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2013 to 2017
$1.7M
Neuro-immune mechanisms in mutant IDH1 gliomasR37NS144573 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro · 2025 to 2026
$1.3M
Chemo-immunotherapy strategy for pediatric high grade gliomaR21NS123879 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G, SCHWENDEMAN, ANNA · 2021 to 2021
$429k
NCI NIH HHS R01 CA243916NIAMS NIH HHS R01 AR078334NINDS NIH HHS R01 NS076991NINDS NIH HHS R01 NS082311NINDS NIH HHS R01 NS096756NINDS NIH HHS R01 NS105556NINDS NIH HHS R01 NS122234NINDS NIH HHS R01 NS122536NINDS NIH HHS R01 NS124167NINDS NIH HHS R21 NS123879NINDS NIH HHS R37 NS094804NINDS NIH HHS R37 NS144573
6 · The paper itself

Abstract

Gliomas with mutant isocitrate dehydrogenase 1 (mIDH1) represent a distinct subgroup of brain tumors characterized by unique metabolic and immunological profiles compared to wildtype IDH1 (wtIDH1) gliomas. Despite recent progress, the cellular mechanisms underlying tumor progression and immune modulation in these subtypes remain poorly understood. In this study, we employed single-cell RNA sequencing (scRNA-seq) to characterize the cellular heterogeneity of wtIDH1 and mIDH1 gliomas, with a particular focus on myeloid cell populations. Our analyses revealed a marked reduction of monocyte-derived tumor-associated macrophages (Mo-TAMs) and lower expression of macrophage migration inhibitory factor (MIF) in mIDH1 gliomas, which was attributable to epigenetic reprogramming. Mechanistic studies using MIF and CD74 knockout mice demonstrated that the MIF-CD74 axis plays a crucial role in regulating the glioma immune microenvironment, thereby driving tumor growth and progression. Importantly, the combination of immune-stimulatory gene therapy (HSV1-thymidine kinase/Fms-like tyrosine kinase 3 ligand; TK/Flt3L) with MIF inhibition significantly extended survival in models of wtIDH1 glioma. These findings highlight the therapeutic potential of targeting the MIF-CD74 pathway and underscore the importance of integrating immunomodulatory strategies for the treatment of glioma.

Identifiers

PMID41648606
PMCPMC12871157

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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.