Evidence map›Paper›PMID 34099731›Full record

ArticleNature communications2021

Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade.

Sebastian R Nielsen, Jan E Strøbech, Edward R Horton, Rene Jackstadt, Anu Laitala, Marina C Bravo, Giorgia Maltese, Adina R D Jensen, Raphael Reuten, Maria Rafaeva and 7 more

Open access · goldAbstract read
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 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

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

  1. A novel regulator in cancer initiation and progression: long noncoding RNA SHNG9.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Pooled it
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  14. Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025
    Review
  15. Review
  16. Transcriptome Landscape of Cancer-Associated Fibroblasts in Human PDAC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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21 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 3 institutions in 3 countries.

Sebastian R Nielsen *Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark. sebastian.nielsen@bric.ku.dk.ORCID http://orcid.org/0000-0002-8449-476X
Jan E Strøbech *Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
Edward R HortonBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-9530-9585
Rene JackstadtCRUK Beatson Institute, Garscube Estate, Glasgow, UK.
Anu LaitalaBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
Marina C BravoBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
Giorgia MalteseBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
Adina R D JensenBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-3739-6320
Raphael ReutenBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-9434-4108
Maria RafaevaBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-7317-4058
Saadia A KarimCRUK Beatson Institute, Garscube Estate, Glasgow, UK.ORCID http://orcid.org/0000-0002-3727-0667
Chang-Il HwangCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.ORCID http://orcid.org/0000-0002-5710-7672
Luis ArnesBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
David A TuvesonCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Owen J SansomCRUK Beatson Institute, Garscube Estate, Glasgow, UK.ORCID http://orcid.org/0000-0001-9540-3010
Jennifer P MortonCRUK Beatson Institute, Garscube Estate, Glasgow, UK.ORCID http://orcid.org/0000-0001-5766-9141
Janine T ErlerBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark. janine.erler@bric.ku.dk.ORCID http://orcid.org/0000-0001-8675-6527
University of Copenhagen · DKCancer Research UK Scotland Institute · GBCold Spring Harbor Laboratory · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Identification of Key Regulators in Pancreatic Cancer MetastasisK22CA226037 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HWANG, CHANG-IL · 2018 to 2020
$486k
The Characterization of the New Tumor Suppressor USP9X in Pancreatic CancerF32CA180717 · NCI · COLD SPRING HARBOR LABORATORY · PI HWANG, CHANG-IL · 2015 to 2017
$179k
Cancer Research UK 21139Cancer Research UK 23390Cancer Research UK 29996Cancer Research UK A17196Cancer Research UK A21139Cancer Research UK A25142Cancer Research UK A25233NCI NIH HHS F32 CA180717NCI NIH HHS K22 CA226037NCI NIH HHS P30 CA045508
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.

Indexed as

AminopyridinesAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Pancreatic DuctalCD8-Positive T-LymphocytesCell Line, TumorDisease Models, AnimalDrug SynergismFemaleHumansImmune Checkpoint InhibitorsLactamsLactams, MacrocyclicLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleAminopyridinesImmune Checkpoint InhibitorsLactamsLactams, MacrocycliclorlatinibPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorPyrazoles

Identifiers

PMID34099731
PMCPMC8184753
OpenAlexW3168416770

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.