Evidence map›Paper›PMID 33214684›Full record

ArticleBritish journal of cancer2021

Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity.

Adan Pinto-Fernandez, Mariolina Salio, Tom Partridge, Jianzhou Chen, George Vere, Helene Greenwood, Cyriel Sebastiaan Olie, Andreas Damianou, Hannah Claire Scott, Henry Jack Pegg and 13 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 57 citations in OpenAlex.

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  14. Deubiquitinases in muscle physiology and disorders.Biochemical Society transactions · 2024
    Review
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  20. USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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

23 authors at 4 institutions in 2 countries.

Adan Pinto-FernandezTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK. adan.pintofernandez@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0003-1693-9664
Mariolina SalioMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0002-4821-3801
Tom PartridgeNuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Jianzhou ChenCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
George VereTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Helene GreenwoodTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Cyriel Sebastiaan OlieTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Andreas DamianouTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Hannah Claire ScottTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Henry Jack PeggCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Alessandra ChiarenzaCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Laura Díaz-SaezTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Paul SmithTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Claudia Gonzalez-LopezMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Bhavisha PatelCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Emma AndertonCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Neil JonesCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Tim R HammondsCRUK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, NW1 0NH, UK.
Kilian HuberTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Ruth MuschelCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Persephone BorrowNuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Vincenzo CerundoloMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Benedikt M KesslerTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, Roosevelt Drive, Oxford, OX3 7FZ, UK. benedikt.kessler@ndm.ox.ac.uk.
University of Oxford · GBMolecular Discovery (United Kingdom) · GBAcademy of Medical Sciences · GBChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

Cancer Research UK 11331Chinese Academy of Medical Sciences (CAMS) 2018-I2M-2-002Medical Research Council MC_U137884181Medical Research Council MR/K012037/1
6 · The paper itself

Abstract

backgroundInterferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo.

methodsIn this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models.

resultsNovel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation.

conclusionsOur results provide strong evidence for USP18 in regulating antigenicity and radiosensitivity, highlighting its potential as a cancer target.

Indexed as

Antigenic VariationCell Line, TumorColorectal NeoplasmsCytokinesGene Knockout TechniquesHCT116 CellsHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveRadiation ToleranceUbiquitinsUbiquitin ThiolesteraseCytokinesISG15 protein, humanUbiquitinsUbiquitin ThiolesteraseUSP18 protein, human

Identifiers

PMID33214684
PMCPMC7884788
OpenAlexW3098982115

What OpenQuestion holds

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LicenceCC BY
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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.