Evidence map›Paper›PMID 33514748›Full record

ArticleNature communications2021

Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth.

Hafsa Munir, James O Jones, Tobias Janowitz, Markus Hoffmann, Maximilien Euler, Carla P Martins, Sarah J Welsh, Jacqueline D Shields

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 1 pooled it
8.8field-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

129 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Neutrophils in cancer.Nature reviews. Cancer · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Engineered bacteria reprogram tumor microenvironmentActa pharmaceutica Sinica. B · 2026
    Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

69 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 4 institutions in 3 countries.

Hafsa MunirMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England.
James O JonesMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England.
Tobias JanowitzCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, 11724, USA.
Markus HoffmannFriedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3, Universitätsstrasse 25a, 91054, Erlangen, Germany.ORCID http://orcid.org/0000-0001-9698-9922
Maximilien EulerFriedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3, Universitätsstrasse 25a, 91054, Erlangen, Germany.
Carla P MartinsMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England.
Sarah J WelshDepartment of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, England.
Jacqueline D ShieldsMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England. js970@mrc-cu.cam.ac.uk.ORCID http://orcid.org/0000-0003-2153-9710
University of Cambridge · GBUniversitätsklinikum Erlangen · DEAstraZeneca (United Kingdom) · GBNorthwell Health · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Cancer Research UK 24868Cancer Research UK C42738/A24868Medical Research Council G101982Medical Research Council MC_UP_1101/2Medical Research Council MC_UU_12022/5NCI NIH HHS P30 CA045508
6 · The paper itself

Abstract

Tumors consist of cancer cells and a network of non-cancerous stroma. Cancer-associated fibroblasts (CAF) are known to support tumorigenesis, and are emerging as immune modulators. Neutrophils release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NET). Here we show that CAFs induce NET formation within the tumor and systemically in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on CAF-derived Amyloid β, a peptide implicated in both neurodegenerative and inflammatory disorders. Inhibition of NETosis in murine tumors skews neutrophils to an anti-tumor phenotype, preventing tumor growth; reciprocally, t-NETs enhance CAF activation. Mirroring observations in mice, CAFs are detected juxtaposed to NETs in human melanoma and pancreatic adenocarcinoma, and show elevated amyloid and β-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.

Indexed as

Amyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsBone MarrowCancer-Associated FibroblastsCarcinogenesisCD11b AntigenCell CommunicationDisease Models, AnimalExtracellular TrapsFemaleHealthy VolunteersHumansMaleMiceMice, TransgenicAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesCD11b Antigenpeptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4Reactive Oxygen Species

Identifiers

PMID33514748
PMCPMC7846803
OpenAlexW3121996996

What OpenQuestion holds

Textmetadata
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.