Evidence map›Paper›PMID 33110073›Full record

ArticleNature communications2020

Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression.

Patricia P Yee, Yiju Wei, Soo-Yeon Kim, Tong Lu, Stephen Y Chih, Cynthia Lawson, Miaolu Tang, Zhijun Liu, Benjamin Anderson, Krishnamoorthy Thamburaj and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 287 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
287citing papers in PubMed, 1 pooled it
27.2field-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

287 citing papers in PubMed, 1 synthesis or guideline pooled it, 397 citations in OpenAlex.

  1. Ferroptosis and Senescence: A Systematic Review.International journal of molecular sciences · 2023
    Pooled it
  2. Review
  3. Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
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  16. Article
  17. Review
  18. Article
  19. Article
  20. Advances and challenges of ferroptosis in tumor immunity.Journal of physiology and biochemistry · 2026
    Review

227 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

17 authors at 1 institution in 1 country.

Patricia P YeeDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0002-3141-2062
Yiju WeiDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Soo-Yeon KimDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0002-8152-3609
Tong LuDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Stephen Y ChihMedical Scientist Training Program, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0003-4397-6065
Cynthia LawsonDivision of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0003-4200-7289
Miaolu TangDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Zhijun LiuDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Benjamin AndersonDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0002-4464-9157
Krishnamoorthy ThamburajDepartment of Radiology, Penn State College of Medicine, Hershey, PA, USA.
Megan M YoungDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Dawit G AregawiDivision of Neuro-Oncology and Skull Base Surgery, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA.
Michael J GlantzDivision of Neuro-Oncology and Skull Base Surgery, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA.
Brad E ZachariaDivision of Neuro-Oncology and Skull Base Surgery, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA.
Charles S SpechtDivision of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Penn State College of Medicine, Hershey, PA, USA.
Hong-Gang WangDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Wei LiDivision of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA. weili@pennstatehealth.psu.edu.ORCID 0000-0001-5696-4309
Penn State Milton S. Hershey Medical Center · US

Funding

Non-canonical Caspase-8 Activation on Autophagosomal MembranesR01CA222349 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI HONG-GANG WANG · 2018 to 2026
$3.0M
Medical Student Training ProgramT32GM118294 · NIGMS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LEVENSON, ROBERT · 2016 to 2021
$1.7M
The role of NONO in TAZ-driven glioma malignant transformationR01NS109147 · NINDS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LI, WEI · 2018 to 2022
$1.7M
Leica SP5 confocal microscope for live-cell imagingS10OD010756 · OD · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI BARNSTABLE, COLIN J · 2012 to 2012
$587k
NCI NIH HHS R01 CA222349NIGMS NIH HHS T32 GM118294NIH HHS S10 OD010756NINDS NIH HHS R01 NS109147
6 · The paper itself

Abstract

Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.

Indexed as

FerroptosisAnimalsCell Line, TumorCoenzyme A LigasesDisease ProgressionFemaleGlioblastomaHumansIronMiceMice, NudeNecrosisNeutrophilsPhospholipid Hydroperoxide Glutathione PeroxidaseAcsl4 protein, mouseCoenzyme A Ligasesglutathione peroxidase 4, mouseIronPhospholipid Hydroperoxide Glutathione Peroxidase

Identifiers

PMID33110073
PMCPMC7591536
OpenAlexW3094771195

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.