Evidence map›Paper›PMID 34771497›Full record

ArticleCancers2021

Neutrophils Extracellular Traps Inhibition Improves PD-1 Blockade Immunotherapy in Colorectal Cancer.

Hongji Zhang, Yu Wang, Amblessed Onuma, Jiayi He, Han Wang, Yujia Xia, Rhea Lal, Xiang Cheng, Gyulnara Kasumova, Zhiwei Hu and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

62 citing papers in PubMed, 78 citations in OpenAlex.

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  14. Neutrophil extracellular traps in cancer.Nature reviews. Cancer · 2026
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2 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

15 authors at 2 institutions in 2 countries.

Hongji ZhangDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-7704-4365
Yu WangDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0003-1251-4159
Amblessed OnumaDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-8757-8475
Jiayi HeDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Han WangDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Yujia XiaDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Rhea LalNeuroscience Undergraduate Division, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0002-8851-414X
Xiang ChengDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Gyulnara KasumovaDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Zhiwei HuDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-0023-1170
Meihong DengDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0003-1901-347X
Joal D BeaneDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Alex C KimDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Hai HuangDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0001-7430-0119
Allan TsungDivision of Surgical Oncology, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
The Ohio State University Wexner Medical Center · USFlorida State University · US

Funding

Surgery triggered immune response and liver metastasesR01CA214865 · NCI · UNIVERSITY OF VIRGINIA · PI Allan Tsung · 2018 to 2026
$3.4M
Endogenous regulators of inflammation in liver ischemia/reperfusionR01GM095566 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TSUNG, ALLAN · 2011 to 2019
$2.7M
Preoperative exercise therapy triggers trained immunity in KCs via cholinergic anti-inflammatory pathwayR01GM137203 · NIGMS · OHIO STATE UNIVERSITY · PI HUANG, HAI · 2020 to 2025
$2.0M
Inhibiting Corneal Neovascularization by Targeting Tissue FactorR21EY037451 · NEI · OHIO STATE UNIVERSITY · PI HU, ZHIWEI, ZHU, HUA · 2025 to 2025
$433k
NCI NIH HHS R01 CA214865NEI NIH HHS R21 EY037451NIGMS NIH HHS R01 GM095566NIGMS NIH HHS R01 GM137203NIH HHS R01-AI152044NIH HHS R01-CA214865-01NIH HHS R01-GM137203NIH HHS R01-GM95566-06NIH HHS T32AI 106704-01A1
6 · The paper itself

Abstract

Immune checkpoint inhibitors can improve the prognosis of patients with advanced malignancy; however, only a small subset of advanced colorectal cancer patients in microsatellite-instability-high or mismatch-repair-deficient colorectal cancer can benefit from immunotherapy. Unfortunately, the mechanism behind this ineffectiveness is unclear. The tumor microenvironment plays a critical role in cancer immunity, and may contribute to the inhibition of immune checkpoint inhibitors and other novel immunotherapies in patients with advanced cancer. Herein, we demonstrate that the DNase I enzyme plays a pivotal role in the degradation of NETs, significantly dampening the resistance to anti-PD-1 blockade in a mouse colorectal cancer model by attenuating tumor growth. Remarkably, DNase I decreases tumor-associated neutrophils and the formation of MC38 tumor cell-induced neutrophil extracellular trap formation in vivo. Mechanistically, the inhibition of neutrophil extracellular traps with DNase I results in the reversal of anti-PD-1 blockade resistance through increasing CD8+ T cell infiltration and cytotoxicity. These findings signify a novel approach to targeting the tumor microenvironment using DNase I alone or in combination with immune checkpoint inhibitors.

Indexed as

CD8+ T cellsDNase Ineutrophils extracellular trapsprogrammed cell death protein 1 (PD-1)

Identifiers

PMID34771497
PMCPMC8582562
OpenAlexW3211138823

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.