Evidence map›Paper›PMID 25658639›Full record

ArticlePloS one2015

Glioma-associated microglia/macrophages display an expression profile different from M1 and M2 polarization and highly express Gpnmb and Spp1.

Frank Szulzewsky, Andreas Pelz, Xi Feng, Michael Synowitz, Darko Markovic, Thomas Langmann, Inge R Holtman, Xi Wang, Bart J L Eggen, Hendrikus W G M Boddeke and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 269 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
269citing papers in PubMed, 1 pooled it
18.9field-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

269 citing papers in PubMed, 1 synthesis or guideline pooled it, 405 citations in OpenAlex.

  1. Pooled it
  2. Oncoimmunology · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Dysregulated Microglial Synaptic Engulfment in Diffuse Midline Glioma.bioRxiv : the preprint server for biology · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Lipid-Metabolically Active TREM2Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  17. Article
  18. Article
  19. Review
  20. Review

209 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

13 authors at 8 institutions in 3 countries.

Frank SzulzewskyMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Andreas PelzMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany; Department of Experimental Neurology, Charité-University Medicine Berlin, Berlin, Germany.
Xi FengDepartment of Neurosciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
Michael SynowitzMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany; Department of Neurosurgery, Charité -Universitätsmedizin Berlin, Berlin, Germany.
Darko MarkovicMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany; Department of Neurosurgery, Helios Clinics, Berlin, Germany.
Thomas LangmannDepartment of Ophthalmology, University of Cologne, Cologne, Germany.
Inge R HoltmanDepartment of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Xi WangMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Bart J L EggenDepartment of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hendrikus W G M BoddekeDepartment of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dolores HambardzumyanDepartment of Neurosciences, Cleveland Clinic, Cleveland, Ohio, United States of America; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
Susanne A WolfMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Helmut KettenmannMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Max Delbrück Center · DEUniversity of Groningen · NLCase Western Reserve University · USCharité - Universitätsmedizin Berlin · DECleveland Clinic · USHelios Hospital Berlin-Buch · DEUniversity Medical Center Groningen · NLUniversity of Cologne · DE

Funding

Non-neoplastic cell types dictate gliomagenesis andU01CA160882 · NCI · EMORY UNIVERSITY · PI HAMBARDZUMYAN, DOLORES, HOLLAND, ERIC C. · 2012 to 2016
$2.8M
NCI NIH HHS U01 CA160882NCI NIH HHS U01CA160882-01A1
6 · The paper itself

Abstract

Malignant glioma belong to the most aggressive neoplasms in humans with no successful treatment available. Patients suffering from glioblastoma multiforme (GBM), the highest-grade glioma, have an average survival time of only around one year after diagnosis. Both microglia and peripheral macrophages/monocytes accumulate within and around glioma, but fail to exert effective anti-tumor activity and even support tumor growth. Here we use microarray analysis to compare the expression profiles of glioma-associated microglia/macrophages and naive control cells. Samples were generated from CD11b+ MACS-isolated cells from naïve and GL261-implanted C57BL/6 mouse brains. Around 1000 genes were more than 2-fold up- or downregulated in glioma-associated microglia/macrophages when compared to control cells. A comparison with published data sets of M1, M2a,b,c-polarized macrophages revealed a gene expression pattern that has only partial overlap with any of the M1 or M2 gene expression patterns. Samples for the qRT-PCR validation of selected M1 and M2a,b,c-specific genes were generated from two different glioma mouse models and isolated by flow cytometry to distinguish between resident microglia and invading macrophages. We confirmed in both models the unique glioma-associated microglia/macrophage phenotype including a mixture of M1 and M2a,b,c-specific genes. To validate the expression of these genes in human we MACS-isolated CD11b+ microglia/macrophages from GBM, lower grade brain tumors and control specimens. Apart from the M1/M2 gene analysis, we demonstrate that the expression of Gpnmb and Spp1 is highly upregulated in both murine and human glioma-associated microglia/macrophages. High expression of these genes has been associated with poor prognosis in human GBM, as indicated by patient survival data linked to gene expression data. We also show that microglia/macrophages are the predominant source of these transcripts in murine and human GBM. Our findings provide new potential targets for future anti-glioma therapy.

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorCells, CulturedGene Expression Regulation, NeoplasticGlioblastomaHumansMacrophagesMembrane GlycoproteinsMiceMicrogliaNeoplasm TransplantationOsteopontinPrognosisGPNMB protein, humanMembrane GlycoproteinsOsteopontinSPP1 protein, human

Identifiers

PMID25658639
PMCPMC4320099
OpenAlexW1970667811

What OpenQuestion holds

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Registered trials

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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.