Evidence map›Paper›PMID 37711611›Full record

ArticleFrontiers in immunology2023

Heparins are potent inhibitors of ectonucleotide pyrophosphatase/phospho-diesterase-1 (NPP1) - a promising target for the immunotherapy of cancer.

Vittoria Lopez, H J Maximilian Schuh, Salahuddin Mirza, Victoria J Vaaßen, Michael S Schmidt, Katharina Sylvester, Riham M Idris, Christian Renn, Laura Schäkel, Julie Pelletier and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
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

16 authors.

Vittoria LopezPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
H J Maximilian SchuhPharmaceutical Institute, Pharmaceutical and Cell Biological Chemistry, University of Bonn, Bonn, Germany.
Salahuddin MirzaPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Victoria J VaaßenPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Michael S SchmidtPharmaceutical Institute, Pharmaceutical and Cell Biological Chemistry, University of Bonn, Bonn, Germany.
Katharina SylvesterPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Riham M IdrisPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Christian RennPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Laura SchäkelPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Julie PelletierCentre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
Jean SévignyCentre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
Annamaria NaggiInstitute for Chemical and Biochemical Research "G. Ronzoni", Milan, Italy.
Björn SchefflerDKFZ Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner site, University Hospital Essen and German Cancer Research Center, Heidelberg, Germany.
Sang-Yong LeePharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.
Gerd BendasPharmaceutical Institute, Pharmaceutical and Cell Biological Chemistry, University of Bonn, Bonn, Germany.
Christa E MüllerPharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Heparins, naturally occurring glycosaminoglycans, are widely used for thrombosis prevention. Upon application as anticoagulants in cancer patients, heparins were found to possess additional antitumor activities. Ectonucleotidases have recently been proposed as novel targets for cancer immunotherapy. Methods and results: In the present study, we discovered that heparin and its derivatives act as potent, selective, allosteric inhibitors of the poorly investigated ectonucleotidase NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1, CD203a). Structure-activity relationships indicated that NPP1 inhibition could be separated from the compounds' antithrombotic effect. Moreover, unfractionated heparin (UFH) and different low molecular weight heparins (LMWHs) inhibited extracellular adenosine production by the NPP1-expressing glioma cell line U87 at therapeutically relevant concentrations. As a consequence, heparins inhibited the ability of U87 cell supernatants to induce CD4+ T cell differentiation into immunosuppressive Treg cells. Discussion: NPP1 inhibition likely contributes to the anti-cancer effects of heparins, and their specific optimization may lead to improved therapeutics for the immunotherapy of cancer.

Indexed as

GliomaHeparinAnticoagulantsHeparin, Low-Molecular-WeightHumansImmunotherapyAnticoagulantsHeparinHeparin, Low-Molecular-Weightadenosineectonucleotidase inhibitorsheparinimmuno-oncologyNPP1U87 glioblastoma cells

Identifiers

PMID37711611
PMCPMC10497752

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Registered trials

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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.