Evidence map›Paper›PMID 25987130›Full record

ArticleOncotarget2015

Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis.

Xi Feng, Frank Szulzewsky, Alexan Yerevanian, Zhihong Chen, David Heinzmann, Rikke Darling Rasmussen, Virginia Alvarez-Garcia, Yeonghwan Kim, Bingcheng Wang, Ilaria Tamagno and 5 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 2% 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

136 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.

  1. Pooled it
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  15. Co-evolution of glioma and immune microenvironment.Journal for immunotherapy of cancer · 2024
    Review
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  17. Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024
    Review
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76 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

15 authors at 6 institutions in 2 countries.

Xi FengDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Frank SzulzewskyCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Alexan YerevanianDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Zhihong ChenDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
David HeinzmannDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Rikke Darling RasmussenDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Virginia Alvarez-GarciaDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Yeonghwan KimDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland, Ohio, USA.
Bingcheng WangRammelkamp Center for Research, MetroHealth Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Ilaria TamagnoDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Hao ZhouDepartment of Immunology at Cleveland Clinic, Cleveland, Ohio, USA.
Xiaoxia LiDepartment of Immunology at Cleveland Clinic, Cleveland, Ohio, USA.
Helmut KettenmannCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Richard M RansohoffDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Dolores HambardzumyanDepartment of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA.
Cleveland Clinic · USMax Delbrück Center · DECalifornia Institute for Regenerative Medicine · USCase Western Reserve University · USMetroHealth Medical Center · USUniversity of Tübingen · DE

Funding

Vascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 1985 to 2019
$32.0M
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 U01CA160882NHLBI NIH HHS P01 HL029582
6 · The paper itself

Abstract

The most abundant populations of non-neoplastic cells in the glioblastoma (GBM) microenvironment are resident microglia, macrophages and infiltrating monocytes from the blood circulation. The mechanisms by which monocytes infiltrate into GBM, their fate following infiltration, and their role in GBM growth are not known. Here we tested the hypothesis that loss of the fractalkine receptor CX3CR1 in microglia and monocytes would affect gliomagenesis. Deletion of Cx3cr1 from the microenvironment resulted in increased tumor incidence and shorter survival times in glioma-bearing mice. Loss of Cx3cr1 did not affect accumulation of microglia/macrophages in peri-tumoral areas, but instead indirectly promoted the trafficking of CD11b+CD45hiCX3CR1lowLy-6ChiLy-6G-F4/80-/low circulating inflammatory monocytes into the CNS, resulting in their increased accumulation in the perivascular area. Cx3cr1-deficient microglia/macrophages and monocytes demonstrated upregulation of IL1β expression that was inversely proportional to Cx3cr1 gene dosage. The Proneural subgroup of the TCGA GBM patient dataset with high IL1β expression showed shorter survival compared to patients with low IL1β. IL1β promoted tumor growth and increased the cancer stem cell phenotype in murine and human Proneural glioma stem cells (GSCs). IL1β activated the p38 MAPK signaling pathway and expression of monocyte chemoattractant protein (MCP-1/CCL2) by tumor cells. Loss of Cx3cr1 in microglia in a monocyte-free environment had no impact on tumor growth and did not alter microglial migration. These data suggest that enhancing signaling to CX3CR1 or inhibiting IL1β signaling in intra-tumoral macrophages can be considered as potential strategies to decrease the tumor-promoting effects of monocytes in Proneural GBM.

Indexed as

AnimalsBrain NeoplasmsCell LineCX3C Chemokine Receptor 1FemaleGene Expression Regulation, NeoplasticGlioblastomaHumansImmunoblottingInterleukin-1betaMacrophagesMaleMice, KnockoutMice, TransgenicMicrogliaMicroscopy, ConfocalCX3C Chemokine Receptor 1CX3CR1 protein, humanCx3cr1 protein, mouseIL1R1 protein, humanInterleukin-1betap38 Mitogen-Activated Protein KinasesReceptors, ChemokineReceptors, Interleukin-1 Type ICX3CR1/CX3CL1 signalingglioblastomamicrogliamonocyte

Identifiers

PMID25987130
PMCPMC4558137
OpenAlexW1791497256

What OpenQuestion holds

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LicenceCC BY
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.