Evidence map›Paper›PMID 31945018›Full record

ArticleThe Journal of clinical investigation2020

Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.

Min Liu, Zan Tong, Chuanlin Ding, Fengling Luo, Shouzhen Wu, Caijun Wu, Sabrin Albeituni, Liqing He, Xiaoling Hu, David Tieri and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 1% 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

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Article
  5. Review
  6. Article
  7. Article
  8. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
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  19. KK2DP7 Stimulates CD11bAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  20. Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 2 countries.

Min LiuDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Zan TongDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Chuanlin DingDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Fengling LuoDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Shouzhen WuDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Caijun WuDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Sabrin AlbeituniDepartment of Microbiology and Immunology, School of Medicine.
Liqing HeDepartment of Chemistry.
Xiaoling HuDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
David TieriDepartment of Anatomical Sciences and Neurobiology, and.
Eric C RouchkaDepartment of Computer Engineering and Computer Science, University of Louisville, Louisville, Kentucky, USA.
Michito HamadaDepartment of Anatomy and Embryology, University of Tsukuba, Ibaraki, Japan.
Satoru TakahashiDepartment of Anatomy and Embryology, University of Tsukuba, Ibaraki, Japan.
Andrew A GibbDivision of Cardiology, Department of Medicine, and.
Goetz KloeckerDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Huang-Ge ZhangDepartment of Microbiology and Immunology, School of Medicine.
Michael BousamraDepartment of Cardiovascular Thoracic Surgery, University of Louisville, Louisville, Kentucky, USA.
Bradford G HillDivision of Cardiology, Department of Medicine, and.
Xiang ZhangDepartment of Chemistry.
Jun YanDivision of Immunotherapy, Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
James Graham Brown Foundation · USEmory University Hospital · USUniversity of Louisville · USUniversity of Tsukuba · JP

Funding

WKU Lead Faculty AwardP20GM103436 · NIGMS · UNIVERSITY OF LOUISVILLE · PI ERIC C ROUCHKA · 2012 to 2026
$60.1M
Systems Biochemistry in Lung Cancer: Toward a Mechanistic Understanding of NSCLCP01CA163223 · NCI · UNIVERSITY OF LOUISVILLE · PI FAN, TERESA WHEI-MEI, FAN, TERESA WHEI-MEI · 2013 to 2017
$6.5M
PILOT PROJECT PROGRAMP30GM106396 · NIGMS · UNIVERSITY OF LOUISVILLE · PI EATON, JOHN W · 2013 to 2017
$5.4M
Transcriptional Regulation of Immunosuppressive Macrophages by c-Maf in CancerR01CA213990 · NCI · UNIVERSITY OF LOUISVILLE · PI YAN, JUN · 2017 to 2021
$1.8M
Ultra Performance Liquid Chromatography High Resolution High Mass Accuracy Mass SpectrometerS10OD020106 · OD · UNIVERSITY OF LOUISVILLE · PI ZHANG, XIANG · 2015 to 2015
$600k
NCI NIH HHS P01 CA163223NCI NIH HHS R01 CA213990NIGMS NIH HHS P20 GM103436NIGMS NIH HHS P30 GM106396NIH HHS S10 OD020106
6 · The paper itself

Abstract

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound β-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.

Indexed as

Immunity, CellularMacrophage ActivationAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMacrophagesMaleMiceMice, KnockoutMonocytesNeoplasms, ExperimentalProto-Oncogene Proteins c-mafMaf protein, mouseProto-Oncogene Proteins c-mafCancerImmunologyImmunotherapyMacrophages

Identifiers

PMID31945018
PMCPMC7108920
OpenAlexW3000546176

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.