Evidence map›Paper›PMID 33964942›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

Interferon- and STING-independent induction of type I interferon stimulated genes during fractionated irradiation.

Ruben S A Goedegebuure, Esther A Kleibeuker, Francesca M Buffa, Kitty C M Castricum, Syed Haider, Iris A Schulkens, Luuk Ten Kroode, Jaap van den Berg, Maarten A J M Jacobs, Anne-Marie van Berkel and 6 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02072720 (Pilot Study to Determine the Effect of Fractionated Radiotherapy on Expression of Pro-angiogenic Factors in Oesophagus Carcinoma), which is not on this map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.8field-weighted citation impact, top 15% 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.

NCT02072720 early_phase1unknown statusnot on this map

Pilot Study to Determine the Effect of Fractionated Radiotherapy on Expression of Pro-angiogenic Factors in Oesophagus Carcinoma

TypeinterventionalSponsorAmsterdam UMC, location VUmcRan2014 to 2021Enrolled40ConditionsPrimary Esophageal CarcinomaArmsBevacizumab
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 31 citations in OpenAlex.

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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

16 authors at 5 institutions in 2 countries.

Ruben S A Goedegebuure *Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4616-5295
Esther A Kleibeuker *Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Francesca M BuffaDepartment of Molecular Oncology, University of Oxford, Oxford, UK.
Kitty C M CastricumDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Syed HaiderDepartment of Molecular Oncology, University of Oxford, Oxford, UK.
Iris A SchulkensDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Luuk Ten KroodeDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Jaap van den BergDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Maarten A J M JacobsDepartment of Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Anne-Marie van BerkelDepartment of Gastroenterology, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands.
Nicole C T van GriekenDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Sarah DerksDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Ben J SlotmanDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Henk M W VerheulDepartment of Medical Oncology, Radboud UMC, Nijmegen, The Netherlands.
Adrian L HarrisDepartment of Molecular Oncology, University of Oxford, Oxford, UK.
Victor L ThijssenDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands. v.thijssen@amsterdamumc.nl.
Amsterdam University Medical Centers · NLUniversity of Oxford · GBOncode Institute · NLNoordwest Ziekenhuisgroep · NLRadboud University Nijmegen · NL

Funding

Cancer Research UK 18974Cancer Research UK 23969
6 · The paper itself

Abstract

backgroundImprovement of radiotherapy efficacy requires better insight in the dynamic responses that occur during irradiation. Here, we aimed to identify the molecular responses that are triggered during clinically applied fractionated irradiation.

methodsGene expression analysis was performed by RNAseq or microarray analysis of cancer cells or xenograft tumors, respectively, subjected to 3-5 weeks of 5 × 2 Gy/week. Validation of altered gene expression was performed by qPCR and/or ELISA in multiple cancer cell lines as well as in pre- and on-treatment biopsies from esophageal cancer patients ( NCT02072720 ). Targeted protein inhibition and CRISPR/Cas-induced gene knockout was used to analyze the role of type I interferons and cGAS/STING signaling pathway in the molecular and cellular response to fractionated irradiation.

resultsGene expression analysis identified type I interferon signaling as the most significantly enriched biological process induced during fractionated irradiation. The commonality of this response was confirmed in all irradiated cell lines, the xenograft tumors and in biopsies from esophageal cancer patients. Time-course analyses demonstrated a peak in interferon-stimulated gene (ISG) expression within 2-3 weeks of treatment. The response was accompanied by a variable induction of predominantly interferon-beta and/or -lambda, but blocking these interferons did not affect ISG expression induction. The same was true for targeted inhibition of the upstream regulatory STING protein while knockout of STING expression only delayed the ISG expression induction.

conclusionsCollectively, the presented data show that clinically applied fractionated low-dose irradiation can induce a delayed type I interferon response that occurs independently of interferon expression or STING signaling. These findings have implications for current efforts that aim to target the type I interferon response for cancer treatment.

Indexed as

AnimalsAstrocytomaCell Line, TumorColonic NeoplasmsDose Fractionation, RadiationEsophageal NeoplasmsFemaleGene Expression Regulation, NeoplasticHT29 CellsHumansImmunityInterferon Type IMembrane ProteinsMiceMice, Inbred BALB CMice, NudeInterferon Type IMembrane ProteinsSTING1 protein, humanSTING ProteinImmune responseRadiotherapyType I interferons

Identifiers

PMID33964942
PMCPMC8106844
OpenAlexW3163829048

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Registered trials

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.