Evidence map›Paper›PMID 37809073›Full record

ArticleFrontiers in immunology2023

TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content.

Sinem Gunalp, Derya Goksu Helvaci, Aysenur Oner, Ahmet Bursalı, Alessandra Conforte, Hüseyin Güner, Gökhan Karakülah, Eva Szegezdi, Duygu Sag

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. A prognostic model based on ScissorTranslational cancer research · 2026
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  8. Immune Biomarker Signature in the Diagnostic Workup of Fever Without Source: A Pilot Study.Mediterranean journal of hematology and infectious diseases · 2026
    Article
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  11. Review
  12. The impact of aspirin on PD-L1 expression and alteration of M2 polarization in non-small cell lung cancer.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  13. Article
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  15. Article
  16. Article
  17. Article
  18. Review
  19. Turkish journal of biology = Turk biyoloji dergisi · 2025
    Article
  20. Review
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

9 authors at 3 institutions in 2 countries.

Sinem GunalpIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Derya Goksu HelvaciIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Aysenur OnerIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Ahmet BursalıIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Alessandra ConforteSchool of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Hüseyin GünerIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Gökhan KarakülahIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Eva SzegezdiSchool of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Duygu SagIzmir Biomedicine and Genome Center, Izmir, Türkiye.
Izmir University · TRDokuz Eylül University · TROllscoil na Gaillimhe – University of Galway · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known. Methods: Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes Results: TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells Conclusions: TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.

Indexed as

Leukemia, Myeloid, AcuteTNF-Related Apoptosis-Inducing LigandHumansMacrophagesPhenotypeReceptors, Death DomainRNA, MessengerTumor MicroenvironmentReceptors, Death DomainRNA, MessengerTNF-Related Apoptosis-Inducing Liganddeath receptorsmacrophage cytotoxicitymacrophage polarizationprimary human macrophagesTRAIL

Identifiers

PMID37809073
PMCPMC10551148
OpenAlexW4386927886

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.