Evidence map›Paper›PMID 31262361›Full record

ArticleJournal for immunotherapy of cancer2019

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21.

Louise M E Müller, Matthew Holmes, Joanne L Michael, Gina B Scott, Emma J West, Karen J Scott, Christopher Parrish, Kathryn Hall, Sina Stäble, Victoria A Jennings and 13 more

Open access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 33 citations in OpenAlex.

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  10. Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
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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 5 institutions in 4 countries.

Louise M E MüllerSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Matthew HolmesSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Joanne L MichaelSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Gina B ScottSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Emma J WestSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Karen J ScottSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Christopher ParrishDepartment of Haematology, St. James's University Hospital, Leeds, UK.
Kathryn HallSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Sina StäbleSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Victoria A JenningsTranslational Immunotherapy Team, The Institute of Cancer Research and Royal Marsden Hospital/Institute of Cancer Research NIHR Biomedical Research Centre, London, UK.
Matthew CullenHaematological Malignancy Diagnostics Service, St. James's University Hospital, Leeds, UK.
Stewart McConnellDepartment of Haematology, St. James's University Hospital, Leeds, UK.
Catherine LangtonDepartment of Haematology, St. James's University Hospital, Leeds, UK.
Emma L TidswellSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Darren ShafrenSchool of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, Australia.
Adel SamsonSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Kevin J HarringtonTranslational Immunotherapy Team, The Institute of Cancer Research and Royal Marsden Hospital/Institute of Cancer Research NIHR Biomedical Research Centre, London, UK.
Hardev PandhaSurrey Cancer Research Institute, Leggett Building, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Christy RalphSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK.
Richard J KellyDepartment of Haematology, St. James's University Hospital, Leeds, UK.
Gordon CookSection of Experimental Haematology, LIMR, University of Leeds, St. James's University Hospital, Leeds, UK.
Alan A MelcherTranslational Immunotherapy Team, The Institute of Cancer Research and Royal Marsden Hospital/Institute of Cancer Research NIHR Biomedical Research Centre, London, UK.
Fiona Errington-MaisSection of Infection and Immunity, Leeds Institute of Medical Research (LIMR), University of Leeds, St. James's University Hospital, Level 5, Wellcome Trust Brenner Building (WTBB), Leeds, LS9 7TF, UK. f.errington@leeds.ac.uk.ORCID 0000-0003-2155-534X
University of Leeds · GBSt James's University Hospital · GBInstitute of Cancer Research · GBUniversity of Newcastle Australia · AUUniversity of Surrey · GB

Funding

Cancer Research UK 21855Cancer Research UK 29039Cancer Research UK A13244Yorkshire Cancer Research L374RA
6 · The paper itself

Abstract

backgroundThe oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible.

methodsThis study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment.

resultsAn Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response.

conclusionThis work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations.

Indexed as

EnterovirusOncolytic VirotherapyOncolytic VirusesAdaptive ImmunityAdultAgedAged, 80 and overCell Line, TumorDendritic CellsFemaleHumansImmunity, InnateIntercellular Adhesion Molecule-1Leukemia, Myeloid, AcuteMaleMiddle AgedICAM1 protein, humanIntercellular Adhesion Molecule-1Adaptive immunityCoxsackievirus A21Innate immunityOncolytic virusesPlasmacytoid DC

Identifiers

PMID31262361
PMCPMC6604201
OpenAlexW2954038428

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.