ArticleNature communications2024
Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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13citing papers in PubMed
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Who cites it
13 citing papers in PubMed.
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
- Human pneumovirus induces IFN-dependent expression of the immune-responsive gene 1 and is inhibited by 4-octyl itaconate in human macrophages.NAR molecular medicine · 2026Article
- NRF2 activators and the inhibitor of nuclear export, selinexor, restrict coronaviruses by targeting a network involving ACE2, TMPRSS2, and XPO1 through an NRF2-independent mechanism.Communications biology · 2026Article
- The Dual Role of Nrf2 Signaling in Virus Infections: Antiviral Guardian or Proviral Accomplice?Pathogens (Basel, Switzerland) · 2025Review
- Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Recent Progress and Emerging Trends.Current oncology (Toronto, Ont.) · 2025Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Targeting TBK1 potentiates oncolytic virotherapy via amplifying ICAM1-mediated NK cell immunity in chemo-resistant colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- Oncolytic Viruses as a Novel Therapeutic Approach for Colorectal Cancer: Mechanisms, Current Advances, and Future Directions.Cancers · 2025Review
- Oncolytic viruses as cancer therapeutics: From mechanistic insights to clinical translation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Total syntheses of cyclohelminthol I-IV reveal a new cysteine-selective covalent reactive group.Chemical science · 2025Article
- Itaconate and its derivatives as anti-pathogenic agents.RSC advances · 2025Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
51 authors.
Naziia KurmashevaDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-9609-5811
Aida SaidDepartment of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Boaz WongDepartment of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.ORCID http://orcid.org/0000-0001-9407-4315
Priscilla KindermanDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-7919-9072
Xiaoying HanLady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.ORCID http://orcid.org/0009-0005-9109-5651
Anna H F RahimicDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Alena KressGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0001-5793-6377
Madalina E Carter-TimofteDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Emilia HolmDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Demi van der HorstDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Christoph F KollmannDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0001-5928-3808
Zhenlong LiuLady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
Chen WangLady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
Huy-Dung HoangDepartment of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Elina KovalenkoDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Maria ChrysopoulouDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0003-4502-5060
Krishna Sundar TwayanaDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Rasmus N OttosenDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
Esben B SvenningsenDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0001-5118-6499
Fabio BegniniDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
Anders E KiibDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-2199-3801
Florian E H KrommDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
Hauke J WeissSchool of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.ORCID http://orcid.org/0000-0002-8265-8644
Daniele Di CarloPasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.
Michela MuscoliniPasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.
Maureen HigginsJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.
Mirte van der HeijdenDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Rozanne ArulanandamOttawa Hospital Research Insitute, Ottawa, ON, K1H 8L6, Canada.
Angelina BardoulCancer Axis, CHUM Research Centre, Montreal, Canada.
Tong TongDepartment of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.ORCID http://orcid.org/0000-0002-8776-3478
Attila OzsvarDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Wen-Hsien HouDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Vivien R SchackDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-1365-3938
Christian K HolmDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-2655-3362
Yunan ZhengSmall Molecule Therapeutics & Platform Technologies, AbbVie Inc., 1 North Waukegon Road, North Chicago, IL, 60064, USA.
Melanie RuzekAbbVie, Bioresearch Center, 100 Research Drive, Worcester, MA, 01608, USA.
Joanna KaluckaDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0003-4887-7672
Laureano de la VegaJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.ORCID http://orcid.org/0000-0003-2707-7414
Walid A M ElgaherDepartment of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, E8.1, 66123, Saarbrücken, Germany.ORCID http://orcid.org/0000-0002-8766-4568
Anders R KorshoejDepartment of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.ORCID http://orcid.org/0000-0003-4285-8171
Rongtuan LinLady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
John HiscottPasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.
Thomas B PoulsenDepartment of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-0763-9996
Luke A O'NeillSchool of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.ORCID http://orcid.org/0000-0002-4333-2748
Dominic G RoyCancer Axis, CHUM Research Centre, Montreal, Canada.ORCID http://orcid.org/0000-0002-6044-0118
Markus M RinschenDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.ORCID http://orcid.org/0000-0002-9252-1342
Nadine van MontfoortDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Jean-Simon DialloDepartment of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.ORCID http://orcid.org/0000-0002-4862-2795
Henner F Farin *Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0003-1558-5366
Tommy Alain *Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.ORCID http://orcid.org/0000-0002-0396-9138
David OlagnierDepartment of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark. olagnier@biomed.au.dk.ORCID http://orcid.org/0000-0001-6912-0674
Funding
Associazione Italiana di Oncologia Medica (Italian Association of Medical Oncology) IG-2019-22891Cancer Research UK 22869Cancer Research UK (CRUK) C52419/A22869Carlsbergfondet (Carlsberg Foundation) CF19-0687Danmarks Grundforskningsfond (Danish National Research Foundation) DNRF164Dansk Kræftforsknings Fond (Danish Cancer Research Fund) R295-A16770Det Frie Forskningsråd (Danish Council for Independent Research) 1026-00003BDet Frie Forskningsråd (Danish Council for Independent Research) 9039-00307BDet Frie Forskningsråd (Danish Council for Independent Research) DFF-37741Hessisches Ministerium für Wissenschaft und Kunst (Hessen State Ministry of Higher Education, Research and the Arts) III L 5 - 519/03/03.001 - (0015)Kræftens Bekæmpelse (Danish Cancer Society) R279-A16218Kræftens Bekæmpelse (Danish Cancer Society) R306-A18092KWF Kankerbestrijding (Dutch Cancer Society) 11056Lundbeckfonden (Lundbeck Foundation) R307-2018-3667Lundbeckfonden (Lundbeck Foundation) R325-2019-1490Lundbeckfonden (Lundbeck Foundation) R335-2019-2138Novo Nordisk Fonden (Novo Nordisk Foundation) NNF19OC0054782Novo Nordisk Fonden (Novo Nordisk Foundation) NNF19OC0056043Novo Nordisk Fonden (Novo Nordisk Foundation) NNF22OC0079512
Abstract
The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.
Indexed as
Oncolytic VirotherapyOncolytic VirusesSuccinatesAnimalsAntiviral AgentsCell Line, TumorColonic NeoplasmsFemaleHumansI-kappa B KinaseInflammationInterferon Type IKelch-Like ECH-Associated Protein 1MiceNF-E2-Related Factor 2NF-kappa BAntiviral AgentsI-kappa B KinaseInterferon Type IKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2NF-kappa BSuccinates
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