Evidence map›Paper›PMID 25537019›Full record

ArticleNeuro-oncology2015

Increasing glioma-associated monocytes leads to increased intratumoral and systemic myeloid-derived suppressor cells in a murine model.

Michael Chae, Timothy E Peterson, Alexis Balgeman, Selby Chen, Lei Zhang, Danielle N Renner, Aaron J Johnson, Ian F Parney

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

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.

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5 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

8 authors at 2 institutions in 1 country.

Michael ChaeDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Timothy E PetersonDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Alexis BalgemanDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Selby ChenDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Lei ZhangDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Danielle N RennerDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Aaron J JohnsonDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Ian F ParneyDepartment of Neurological Surgery (M.C., T.E.P., A.B., S.C., L.Z., I.F.P.) and Department of Immunology, Mayo Clinic, Rochester, Minnesota (D.N.R., A.J.J.).
Neurological Surgery · USMayo Clinic · US

Funding

Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
Enhancing Glioma-Specific ImmunityR21CA186976 · NCI · MAYO CLINIC ROCHESTER · PI JOHNSON, AARON J · 2014 to 2015
$380k
NCI NIH HHS 1P50CA108961-06NCI NIH HHS P50 CA108961NCI NIH HHS R21 CA186976
6 · The paper itself

Abstract

backgroundPatients with glioblastoma multiforme (GBM) exhibit marked intratumoral and systemic immunosuppression. GBM is heavily infiltrated with monocytic cells. Monocytes contacting GBM cells develop features of immunosuppressive myeloid-derived suppressor cells (MDSCs), which are elevated in GBM patients. Therefore, we hypothesized that circulating MDSC levels could be raised in vivo by increasing glioma-associated macrophages.

methodsGL261-luciferase glioma was implanted intracranially in C57BL/6 mice with or without additional normal syngeneic CD11b+ monocytes. Tumor growth and intratumoral and systemic MDSC (CD11b+/Gr-1+) levels were determined. Green fluorescent protein (GFP)-transgenic monocytes were coinjected intracranially with GL261-luciferase cells. GFP+ cell frequency among splenic and bone marrow MDSCs was determined. Impact of increased MDSC's on spontaneous immune responses to tumor cells expressing a model antigen (ovalbumin [OVA]) was determined.

resultsTumors grew faster and MDSC's were increased in tumor, spleen, and bone marrow in mice receiving GL261-Luc plus monocytes. Many (30%-50%) systemic MDSC's were GFP+ in mice receiving intracranial tumor plus GFP-transgenic monocytes, suggesting that they originated from glioma-associated monocytes. Tumor-infiltrating OVA-specific CD8+ T cells were markedly reduced in mice receiving GL261-OVA and monocytes compared with mice receiving GL261-OVA alone.

conclusionsIncreasing glioma-associated macrophages in intracranial GL261 glioma decreases survival and markedly increases intratumoral and systemic MDSC's, many of which originate directly from glioma-associated macrophages. This is associated with decreased spontaneous immune responses to a model antigen. To our knowledge, this is the first evidence in cancer that systemic MDSC's can arise directly from normal monocytes that have undergone intratumoral immunosuppressive education.

Indexed as

AnimalsBone Marrow CellsBrain NeoplasmsCell Line, TumorDisease Models, AnimalGliomaMiceMice, Inbred C57BLMyeloid CellsSpleenGL261gliomaimmunosuppressionmyeloid-derived suppressor celltumor-associated macrophage

Identifiers

PMID25537019
PMCPMC5654350
OpenAlexW2325587933

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.