Evidence map›Paper›PMID 34485907›Full record

ArticleNeuro-oncology advances

Inhibition of microglial EZH2 leads to anti-tumoral effects in pediatric diffuse midline gliomas.

Lily Keane, Mathilde Cheray, Dalel Saidi, Caoimhe Kirby, Lara Friess, Patricia Gonzalez-Rodriguez, Maren Elisabeth Gerdes, Kathleen Grabert, Barry W McColl, Bertrand Joseph

Open access · goldAbstract read
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

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  5. Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025
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  16. Microglia and Brain Macrophages as Drivers of Glioma Progression.International journal of molecular sciences · 2022
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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 at 2 institutions in 2 countries.

Lily KeaneInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Mathilde CherayInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Dalel SaidiInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Caoimhe KirbyUK Dementia Research Institute, Center for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Lara FriessInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Patricia Gonzalez-RodriguezInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Maren Elisabeth GerdesInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Kathleen GrabertInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Barry W McCollUK Dementia Research Institute, Center for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Bertrand JosephInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEUK Dementia Research Institute · GB

Funding

Medical Research Council G0701018Medical Research Council G1100578Medical Research Council MR/N004272/1Wellcome Trust
6 · The paper itself

Abstract

backgroundDiffuse intrinsic pontine gliomas (DIPG), within diffuse midline gliomas are aggressive pediatric brain tumors characterized by histone H3-K27M mutation. Small-molecule inhibitors for the EZH2-H3K27 histone methyltransferase have shown promise in preclinical animal models of DIPG, despite having little effect on DIPG cells

methodsPrimary DIPG tissues, and cocultures between microglia and patient-derived DIPG or -pediatric high-grade glioma (pHGG) cell lines, were used to establish the H3-K27M status of each cell type. Antisense RNA strategies were used to target

resultsIn primary DIPG tissues, microglia do not carry the H3-K27M mutation, otherwise characteristic of the cancer cells. Activation of a microglial tumor-supportive phenotype by pHGG, independently of their H3-K27M status, is associated with a transient H3K27me3 downregulation. Repression of EZH2 in DIPG cells has no impact on tumor cell survival or their ability to activate microglia. However, repression of EZH2 in microglia induces an anti-tumor phenotype resulting in decreased cancer cell invasion capability, increased microglial phagocytosis, and tumor-related cell death.

conclusionsThese results indicate that microglia, beyond the tumor cells, contribute to the observed response of DIPG to EZH2 inhibition. Results highlight the potential importance of microglia as a new therapeutic avenue in DIPG.

Indexed as

anti-tumoralDIPGEZH2H3K27me3microglia

Identifiers

PMID34485907
PMCPMC8409254
OpenAlexW3177775207

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.