Evidence map›Paper›PMID 33796407›Full record

ArticleOncoimmunology2021

Re-polarization of immunosuppressive macrophages to tumor-cytotoxic macrophages by repurposed metabolic drugs.

Cesar Oyarce, Ana Vizcaino-Castro, Shipeng Chen, Annemarie Boerma, Toos Daemen

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

Article in Oncoimmunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 59 citations in OpenAlex.

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  3. DCC-2036 induces repolarization of TAMs to M1 type and enhances CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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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

5 authors at 1 institution in 1 country.

Cesar OyarceDepartment of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-0078-3282
Ana Vizcaino-CastroDepartment of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Shipeng ChenDepartment of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Annemarie BoermaDepartment of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Toos DaemenDepartment of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-0166-512X
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

M2-like tumor-associated macrophages promote tumor progression by establishing an immunosuppressive tumor microenvironment. The phenotype and activity of immunosuppressive macrophages are related to their mitochondrial metabolism. Thus, we studied if drugs targeting mitochondrial metabolic pathways can repolarize macrophages from M2 into an M1-like phenotype or can prevent M0-to-M2 polarization. The drugs selected are clinically approved or in clinical trials and target M2-specific metabolic pathways: fatty acid oxidation (Perhexiline and Trimetazidine), glutaminolysis (CB-839), PPAR activation (HX531), and mitochondrial electron transport chain (VLX-600). Murine bone marrow-derived macrophages were either polarized to M2 using IL-4 in the presence of the drugs or polarized first into M2 and then treated with the drugs in presence of IFN-γ for re-polarization. Targeting both fatty acid oxidation with Perhexiline or the electron transport chain with VLX-600 in the presence of IFN-γ, impaired mitochondrial basal, and maximal respiration and resulted in M2 to M1-like re-polarization (increased iNOS expression, NO production, IL-23, IL-27, and TNF-α secretion), similar to LPS+IFN-γ re-polarization. Moreover, drug-induced macrophage re-polarization resulted in a strong tumor-cytotoxic activity. Furthermore, the polarization of M0- to M2-like macrophages was impaired by CB-839, Trimetazidine, HX531, and Perhexiline, while Hx531 and Perhexiline also reduced MCP-1 secretion. Our results show that by targeting cell metabolism, macrophages could be re-polarized from M2- into an anti-tumoral M1-like phenotype and that M0-to-M2 polarization could be prevented. Overall, this study provides rational for the use of clinically applicable drugs to change an immunosuppressive tumor environment into a pro-inflammatory tumor environment that could support cancer immunotherapies.

Indexed as

NeoplasmsPharmaceutical PreparationsAnimalsCell CommunicationMacrophage ActivationMacrophagesMiceTumor MicroenvironmentPharmaceutical PreparationsimmunometabolismMacrophage polarizationmacrophage re-polarizationmitochondrial respiration

Identifiers

PMID33796407
PMCPMC7971325
OpenAlexW3137753512

What OpenQuestion holds

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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.