Evidence map›Paper›PMID 30016493›Full record

ArticleQJM : monthly journal of the Association of Physicians2018

Oral squamous carcinoma cells promote macrophage polarization in an MIF-dependent manner.

M Barbosa de Souza Rizzo, M Brasilino de Carvalho, E J Kim, B E Rendon, J T Noe, A Darlene Wise, R A Mitchell

Open access · bronzeAbstract read
In one paragraph

Article in QJM : monthly journal of the Association of Physicians, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

24 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  5. Spatial Profiling Identifies Tumor-Associated Stroma Enrichment and MIF as Potential Immunotherapy Targets in Primary Ewing Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
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  7. Review
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  11. Immunosuppressive MFAP2Cellular oncology (Dordrecht, Netherlands) · 2024
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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

7 authors at 2 institutions in 2 countries.

M Barbosa de Souza RizzoDepartment of Radiology and Oncology, Medical School, University of Sao Paulo, São Paulo, São Paulo, Brazil.
M Brasilino de CarvalhoDepartment of Radiology and Oncology, Medical School, University of Sao Paulo, São Paulo, São Paulo, Brazil.
E J KimJ.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA.
B E RendonJ.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA.
J T NoeJ.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA.
A Darlene WiseJ.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA.
R A MitchellJ.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA.
University of Louisville · USUniversidade de São Paulo · BR

Funding

Small molecule targeting of MIF as a novel melanoma therapeuticR01CA186661 · NCI · UNIVERSITY OF LOUISVILLE · PI MITCHELL, ROBERT A · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA186661
6 · The paper itself

Abstract

backgroundTumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, extracellular matrix remodeling and dysregulated tumor cell proliferation. Our prior studies revealed that macrophage-derived, but not tumor cell-derived, macrophage migration inhibitory factor (MIF), is an important determinant of TAM alternative activation and M2 polarization.

aimBecause MIF is historically thought to initiate signaling via a receptor-dependent, outside-in mode of action, we wished to investigate the specific contributions of tumor-derived vs. macrophage-derived MIF to M2 marker expression during macrophage polarization.

designMurine oral squamous cell-carcinoma cells (SCCVII) were co-cultured with either the RAW 264.7 mouse macrophage cell line or mouse primary bone marrow-derived macrophages in the context of MIF genetic loss/inhibition individually or in combination each cell type.

methodsTwelve well Transwell plates were used to co-culture SCCVII cells and RAW 264.7, MIF+/+ or MIF-/- macrophages treated with/without the small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine and incubated in the presence or absence of interleukin (IL-4) for 48 h. Macrophages were analyzed by quantitative real-time polymerase chain reaction and/or immunoblotting for relative macrophage polarization marker expression.

resultsIL-4 treatment synergizes with SCCVII co-culture in inducing the expression of macrophage M2 markers and loss or inhibition of macrophage-derived MIF significantly reduces both IL-4 alone and IL-4/SCCVII co-culture-induced macrophage M2 marker expression.

conclusionThese studies identify an important and dominant requirement for macrophage MIF in maximal Th2-cytokine and oral squamous carcinoma cell-induced macrophage polarization and M2 marker expression.

Indexed as

AnimalsCarcinoma, Squamous CellCell Line, TumorCell ProliferationCoculture TechniquesInterleukin-4Intramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMacrophagesMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicPyrimidinesRAW 264.7 Cells4-iodo-6-phenylpyrimidineInterleukin-4Intramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMif protein, mousePyrimidines

Identifiers

PMID30016493
PMCPMC6217709
OpenAlexW2884701884

What OpenQuestion holds

Textmetadata
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.