Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.

Animals Humans Oncolytic Virotherapy / methods Succinates / pharmacology Mice Cell Line, Tumor Oncolytic Viruses Interferon Type I / metabolism NF-E2-Related Factor 2 / metabolism Colonic Neoplasms / therapy Antiviral Agents / pharmacology NF-kappa B / metabolism I-kappa B Kinase / metabolism Kelch-Like ECH-Associated Protein 1 / metabolism Inflammation / drug therapy Female Vesicular stomatitis Indiana virus / physiology Signal Transduction / drug effects

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 May 2024
Historique:
received: 07 06 2023
accepted: 23 04 2024
medline: 16 5 2024
pubmed: 16 5 2024
entrez: 15 5 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-48422-x PMID: 38750019
pubmed: 38750019
doi: 10.1038/s41467-024-48422-x
pii: 10.1038/s41467-024-48422-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4096

Subventions

Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R335-2019-2138
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R325-2019-1490
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R307-2018-3667
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R325-2019-1490
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF22OC0079512
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF19OC0054782
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF19OC0056043
Organisme : Kræftens Bekæmpelse (Danish Cancer Society)
ID : R279-A16218
Organisme : Kræftens Bekæmpelse (Danish Cancer Society)
ID : R306-A18092
Organisme : Danmarks Grundforskningsfond (Danish National Research Foundation)
ID : DNRF164
Organisme : Det Frie Forskningsråd (Danish Council for Independent Research)
ID : 1026-00003B
Organisme : Det Frie Forskningsråd (Danish Council for Independent Research)
ID : DFF-37741
Organisme : Det Frie Forskningsråd (Danish Council for Independent Research)
ID : 9039-00307B
Organisme : Carlsbergfondet (Carlsberg Foundation)
ID : CF19-0687
Organisme : Cancer Research UK (CRUK)
ID : C52419/A22869
Organisme : Dansk Kræftforsknings Fond (Danish Cancer Research Fund)
ID : R295-A16770
Organisme : Associazione Italiana di Oncologia Medica (Italian Association of Medical Oncology)
ID : IG-2019-22891
Organisme : KWF Kankerbestrijding (Dutch Cancer Society)
ID : 11056
Organisme : Hessisches Ministerium für Wissenschaft und Kunst (Hessen State Ministry of Higher Education, Research and the Arts)
ID : III L 5 - 519/03/03.001 - (0015)

Informations de copyright

© 2024. The Author(s).

Références

Swift, S. L. & Stojdl, D. F. Big data offers novel insights for oncolytic virus immunotherapy. Viruses 8, 45 (2016).
pubmed: 26861383 pmcid: 4776200 doi: 10.3390/v8020045
Macedo, N., Miller, D. M., Haq, R. & Kaufman, H. L. Clinical landscape of oncolytic virus research in 2020. J. Immunother. Cancer 8, e001486 (2020).
pubmed: 33046622 pmcid: 7552841 doi: 10.1136/jitc-2020-001486
Cook, M. & Chauhan, A. Clinical application of oncolytic viruses: a systematic review. Int. J. Mol. Sci. 21, 7505 (2020).
pubmed: 33053757 pmcid: 7589713 doi: 10.3390/ijms21207505
Pol, J. G., Workenhe, S. T., Konda, P., Gujar, S. & Kroemer, G. Cytokines in oncolytic virotherapy. Cytokine Growth Factor Rev. 56, 4–27 (2020).
pubmed: 33183957 doi: 10.1016/j.cytogfr.2020.10.007
Twumasi-Boateng, K., Pettigrew, J. L., Kwok, Y. Y. E., Bell, J. C. & Nelson, B. H. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat. Rev. Cancer 18, 419–432 (2018).
pubmed: 29695749 doi: 10.1038/s41568-018-0009-4
Engeland, C. E. & Bell, J. C. Introduction to oncolytic virotherapy. Methods Mol. Biol. 2058, 1–6 (2020).
pubmed: 31486028 doi: 10.1007/978-1-4939-9794-7_1
Lichty, B. D., Breitbach, C. J., Stojdl, D. F. & Bell, J. C. Going viral with cancer immunotherapy. Nat. Rev. Cancer 14, 559–567 (2014).
pubmed: 24990523 doi: 10.1038/nrc3770
Rehman, H., Silk, A. W., Kane, M. P. & Kaufman, H. L. Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy. J. Immunother. Cancer 4, 53 (2016).
pubmed: 27660707 pmcid: 5029010 doi: 10.1186/s40425-016-0158-5
Todo, T. et al. Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nat. Med. 28, 1630–1639 (2022).
pubmed: 35864254 pmcid: 9388376 doi: 10.1038/s41591-022-01897-x
Liikanen, I. et al. Induction of interferon pathways mediates in vivo resistance to oncolytic adenovirus. Mol. Ther. 19, 1858–1866 (2011).
pubmed: 21792178 pmcid: 3188743 doi: 10.1038/mt.2011.144
Liu, Y. P., Suksanpaisan, L., Steele, M. B., Russell, S. J. & Peng, K. W. Induction of antiviral genes by the tumor microenvironment confers resistance to virotherapy. Sci. Rep. 3, 2375 (2013).
pubmed: 23921465 pmcid: 3736178 doi: 10.1038/srep02375
Russell, S. J., Peng, K. W. & Bell, J. C. Oncolytic virotherapy. Nat. Biotechnol. 30, 658–670 (2012).
pubmed: 22781695 pmcid: 3888062 doi: 10.1038/nbt.2287
Fulci, G. et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc. Natl Acad. Sci. USA 103, 12873–12878 (2006).
pubmed: 16908838 pmcid: 1568940 doi: 10.1073/pnas.0605496103
Hasegawa, N. et al. Cyclophosphamide enhances antitumor efficacy of oncolytic adenovirus expressing uracil phosphoribosyltransferase (UPRT) in immunocompetent Syrian hamsters. Int. J. Cancer 133, 1479–1488 (2013).
pubmed: 23444104 doi: 10.1002/ijc.28132
Alain, T. et al. Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production. Proc. Natl Acad. Sci. USA 107, 1576–1581 (2010).
pubmed: 20080710 pmcid: 2824402 doi: 10.1073/pnas.0912344107
Nguyen, T. L. et al. Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. Proc. Natl Acad. Sci. USA 105, 14981–14986 (2008).
pubmed: 18815361 pmcid: 2567479 doi: 10.1073/pnas.0803988105
Arulanandam, R. et al. Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing. Nat. Commun. 6, 6410 (2015).
pubmed: 25817275 doi: 10.1038/ncomms7410
Zakaria, C. et al. Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E/4E-BP axis. PLoS Pathog. 14, e1007264 (2018).
pubmed: 30138450 pmcid: 6124814 doi: 10.1371/journal.ppat.1007264
Wong, B. et al. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVDelta51 oncolytic virotherapy. Mol. Ther. 31, 3176–3192 (2023).
pubmed: 37766429 doi: 10.1016/j.ymthe.2023.09.017
Olagnier, D. et al. Activation of Nrf2 signaling augments vesicular stomatitis virus oncolysis via autophagy-driven suppression of antiviral immunity. Mol. Ther. 25, 1900–1916 (2017).
pubmed: 28527723 pmcid: 5542709 doi: 10.1016/j.ymthe.2017.04.022
Selman, M. et al. Dimethyl fumarate potentiates oncolytic virotherapy through NF-kappaB inhibition. Sci. Transl. Med. 10, eaao1613 (2018).
pubmed: 29367345 doi: 10.1126/scitranslmed.aao1613
Bambouskova, M. et al. Electrophilic properties of itaconate and derivatives regulate the IkappaBzeta-ATF3 inflammatory axis. Nature 556, 501–504 (2018).
pubmed: 29670287 pmcid: 6037913 doi: 10.1038/s41586-018-0052-z
Mills, E. L. et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556, 113–117 (2018).
pubmed: 29590092 pmcid: 6047741 doi: 10.1038/nature25986
Lampropoulou, V. et al. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab. 24, 158–166 (2016).
pubmed: 27374498 pmcid: 5108454 doi: 10.1016/j.cmet.2016.06.004
Olagnier, D. et al. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming. Nat. Commun. 9, 3506 (2018).
pubmed: 30158636 pmcid: 6115435 doi: 10.1038/s41467-018-05861-7
He, W. et al. Mesaconate is synthesized from itaconate and exerts immunomodulatory effects in macrophages. Nat. Metab. 4, 524–533 (2022).
pubmed: 35655024 pmcid: 9744384 doi: 10.1038/s42255-022-00565-1
Chen, F. et al. Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism. Nat. Metab. 4, 534–546 (2022).
pubmed: 35655026 pmcid: 9170585 doi: 10.1038/s42255-022-00577-x
Swain, A. et al. Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat. Metab. 2, 594–602 (2020).
pubmed: 32694786 pmcid: 7378276 doi: 10.1038/s42255-020-0210-0
Runtsch, M. C. et al. Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. Cell Metab. 34, 487–501.e488 (2022).
pubmed: 35235776 doi: 10.1016/j.cmet.2022.02.002
Hooftman, A. et al. The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 32, 468–478.e467 (2020).
pubmed: 32791101 pmcid: 7422798 doi: 10.1016/j.cmet.2020.07.016
Bambouskova, M. et al. Itaconate confers tolerance to late NLRP3 inflammasome activation. Cell Rep. 34, 108756 (2021).
pubmed: 33691097 pmcid: 8039864 doi: 10.1016/j.celrep.2021.108756
Li, W. et al. 4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING. Cell Rep. 42, 112145 (2023).
pubmed: 36862550 doi: 10.1016/j.celrep.2023.112145
Su, C., Cheng, T., Huang, J., Zhang, T. & Yin, H. 4-Octyl itaconate restricts STING activation by blocking its palmitoylation. Cell Rep. 42, 113040 (2023).
pubmed: 37624697 doi: 10.1016/j.celrep.2023.113040
Olagnier, D. et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat. Commun. 11, 4938 (2020).
pubmed: 33009401 pmcid: 7532469 doi: 10.1038/s41467-020-18764-3
Ribo-Molina, P. et al. 4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1. J. Virol. 97, e0132523 (2023).
pubmed: 37823646 doi: 10.1128/jvi.01325-23
Waqas, F. H. et al. NRF2 activators inhibit influenza A virus replication by interfering with nucleo-cytoplasmic export of viral RNPs in an NRF2-independent manner. PLoS Pathog. 19, e1011506 (2023).
pubmed: 37459366 pmcid: 10374058 doi: 10.1371/journal.ppat.1011506
Sohail, A. et al. Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog. 18, e1010219 (2022).
pubmed: 35025971 pmcid: 8846506 doi: 10.1371/journal.ppat.1010219
Carter, M. E. et al. A three-dimensional organoid model of primary breast cancer to investigate the effects of oncolytic virotherapy. Front. Mol. Biosci. 9, 826302 (2022).
pubmed: 35223990 pmcid: 8874275 doi: 10.3389/fmolb.2022.826302
Raimondi, G. et al. Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses. EBioMedicine 56, 102786 (2020).
pubmed: 32460166 pmcid: 7251378 doi: 10.1016/j.ebiom.2020.102786
Farin, H. F. et al. Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses. Cancer Discov. 13, 2192–2211 (2023).
pubmed: 37489084 pmcid: 10551667 doi: 10.1158/2159-8290.CD-23-0050
Louth, E. L., Jorgensen, R. L., Korshoej, A. R., Sorensen, J. C. H. & Capogna, M. Dopaminergic neuromodulation of spike timing dependent plasticity in mature adult rodent and human cortical neurons. Front. Cell Neurosci. 15, 668980 (2021).
pubmed: 33967700 pmcid: 8102156 doi: 10.3389/fncel.2021.668980
Qin, W. et al. Chemoproteomic profiling of itaconation by bioorthogonal probes in inflammatory macrophages. J. Am. Chem. Soc. 142, 10894–10898 (2020).
pubmed: 32496768 doi: 10.1021/jacs.9b11962
Taguchi, K. & Yamamoto, M. The KEAP1-NRF2 system as a molecular target of cancer treatment. Cancers 13, 46 (2020).
pubmed: 33375248 pmcid: 7795874 doi: 10.3390/cancers13010046
He, F., Antonucci, L. & Karin, M. NRF2 as a regulator of cell metabolism and inflammation in cancer. Carcinogenesis 41, 405–416 (2020).
pubmed: 32347301 pmcid: 7298623 doi: 10.1093/carcin/bgaa039
Finkelshtein, D., Werman, A., Novick, D., Barak, S. & Rubinstein, M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc. Natl Acad. Sci. USA 110, 7306–7311 (2013).
pubmed: 23589850 pmcid: 3645523 doi: 10.1073/pnas.1214441110
Stojdl, D. F. et al. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell 4, 263–275 (2003).
pubmed: 14585354 doi: 10.1016/S1535-6108(03)00241-1
Chiang, C. et al. Sequence-specific modifications enhance the broad-spectrum antiviral response activated by RIG-I agonists. J. Virol. 89, 8011–8025 (2015).
pubmed: 26018150 pmcid: 4505665 doi: 10.1128/JVI.00845-15
Beljanski, V. et al. Enhanced influenza virus-like particle vaccination with a structurally optimized RIG-I agonist as adjuvant. J. Virol. 89, 10612–10624 (2015).
pubmed: 26269188 pmcid: 4580177 doi: 10.1128/JVI.01526-15
Sato, Y., Fu, Y., Liu, H., Lee, M. Y. & Shaw, M. H. Tumor-immune profiling of CT-26 and Colon 26 syngeneic mouse models reveals mechanism of anti-PD-1 response. BMC Cancer 21, 1222 (2021).
pubmed: 34774008 pmcid: 8590766 doi: 10.1186/s12885-021-08974-3
McNab, F., Mayer-Barber, K., Sher, A., Wack, A. & O’Garra, A. Type I interferons in infectious disease. Nat. Rev. Immunol. 15, 87–103 (2015).
pubmed: 25614319 pmcid: 7162685 doi: 10.1038/nri3787
Shulak, L. et al. Histone deacetylase inhibitors potentiate vesicular stomatitis virus oncolysis in prostate cancer cells by modulating NF-kappaB-dependent autophagy. J. Virol. 88, 2927–2940 (2014).
pubmed: 24371063 pmcid: 3958113 doi: 10.1128/JVI.03406-13
Liu, S. et al. Crystal structure of a human IkappaB kinase beta asymmetric dimer. J. Biol. Chem. 288, 22758–22767 (2013).
pubmed: 23792959 pmcid: 3829360 doi: 10.1074/jbc.M113.482596
Rushe, M. et al. Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site. Structure 16, 798–808 (2008).
pubmed: 18462684 doi: 10.1016/j.str.2008.02.012
Chen, L. L. et al. Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses. Nat Cell Biol 24, 353–363 (2022).
pubmed: 35256775 pmcid: 9305987 doi: 10.1038/s41556-022-00853-8
Bhatt, D. K., Chammas, R. & Daemen, T. Resistance mechanisms influencing oncolytic virotherapy, a systematic analysis. Vaccines 9, 1166 (2021).
pubmed: 34696274 pmcid: 8537623 doi: 10.3390/vaccines9101166
Thimmulappa, R. K. et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 116, 984–995 (2006).
pubmed: 16585964 pmcid: 1421348 doi: 10.1172/JCI25790
Varble, A. J. et al. The vesicular stomatitis virus matrix protein inhibits NF-kappaB activation in mouse L929 cells. Virology 499, 99–104 (2016).
pubmed: 27643886 doi: 10.1016/j.virol.2016.09.009
Horner, S. M., Park, H. S. & Gale, M. Jr. Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix alpha0. J. Virol. 86, 3112–3120 (2012).
pubmed: 22238314 pmcid: 3302330 doi: 10.1128/JVI.06727-11
Zhao, T. et al. The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways. Nat. Immunol. 8, 592–600 (2007).
pubmed: 17468758 doi: 10.1038/ni1465
Wang, Q. et al. The anti-inflammatory drug dimethyl itaconate protects against colitis-associated colorectal cancer. J. Mol. Med. 98, 1457–1466 (2020).
pubmed: 32840638 doi: 10.1007/s00109-020-01963-2
Zhan, Z., Wang, Z., Bao, Y., Liu, W. & Hong, L. OI inhibits development of ovarian cancer by blocking crosstalk between cancer cells and macrophages via HIF-1alpha pathway. Biochem. Biophys. Res. Commun. 606, 142–148 (2022).
pubmed: 35358838 doi: 10.1016/j.bbrc.2022.03.106
Bhatt, D. K., Janzen, T., Daemen, T. & Weissing, F. J. Modelling the spatial dynamics of oncolytic virotherapy in the presence of virus-resistant tumour cells. PLoS Comput. Biol. 18, e1010076 (2022).
pubmed: 36473017 pmcid: 9767357 doi: 10.1371/journal.pcbi.1010076
Berg, D. R. et al. In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics. PLoS Comput. Biol. 15, e1006773 (2019).
pubmed: 30835721 pmcid: 6400333 doi: 10.1371/journal.pcbi.1006773
Torrente, L. et al. Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses. Oncogene 36, 6204–6212 (2017).
pubmed: 28692050 pmcid: 5641449 doi: 10.1038/onc.2017.221
van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015).
pubmed: 25957691 pmcid: 6428276 doi: 10.1016/j.cell.2015.03.053
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 2191–2194 (2013).
doi: 10.1001/jama.2013.281053
Louis, D. N. et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 23, 1231–1251 (2021).
pubmed: 34185076 pmcid: 8328013 doi: 10.1093/neuonc/noab106
Ting, J. T. et al. A robust ex vivo experimental platform for molecular-genetic dissection of adult human neocortical cell types and circuits. Sci. Rep. 8, 8407 (2018).
pubmed: 29849137 pmcid: 5976666 doi: 10.1038/s41598-018-26803-9
Lee, B. R. et al. Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex. Science 382, eadf6484 (2023).
pubmed: 37824669 doi: 10.1126/science.adf6484
Hoang, H. D. et al. Induction of an alternative mRNA 5’ leader enhances translation of the ciliopathy gene Inpp5e and resistance to oncolytic virus infection. Cell Rep. 29, 4010–4023.e4015 (2019).
pubmed: 31851930 doi: 10.1016/j.celrep.2019.11.072
Leber, M. F. et al. Sequencing of serially passaged measles virus affirms its genomic stability and reveals a nonrandom distribution of consensus mutations. J. Gen. Virol. 101, 399–409 (2020).
pubmed: 32053093 doi: 10.1099/jgv.0.001395
Schnalzger, T. E. et al. 3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids. EMBO J. 38, e100928 (2019).
pubmed: 31036555 pmcid: 6576164 doi: 10.15252/embj.2018100928
Groeneveldt, C. et al. Preconditioning of the tumor microenvironment with oncolytic reovirus converts CD3-bispecific antibody treatment into effective immunotherapy. J. Immunother. Cancer https://doi.org/10.1136/jitc-2020-001191 (2020).
Belkina, A. C. et al. Automated optimized parameters for T-distributed stochastic neighbor embedding improve visualization and analysis of large datasets. Nat. Commun. 10, 5415 (2019).
pubmed: 31780669 pmcid: 6882880 doi: 10.1038/s41467-019-13055-y
Jeon, S. A. et al. Comparison of the MGISEQ-2000 and Illumina HiSeq 4000 sequencing platforms for RNA sequencing. Genom. Inform. 17, e32 (2019).
doi: 10.5808/GI.2019.17.3.e32
Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357–360 (2015).
pubmed: 25751142 pmcid: 4655817 doi: 10.1038/nmeth.3317
Pertea, M. et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol 33, 290–295 (2015).
pubmed: 25690850 pmcid: 4643835 doi: 10.1038/nbt.3122
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
pubmed: 19910308 doi: 10.1093/bioinformatics/btp616
Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017).
pubmed: 29184056 pmcid: 5705698 doi: 10.1038/s41467-017-01261-5
Gearing, L. J. et al. CiiiDER: a tool for predicting and analysing transcription factor binding sites. PLoS ONE 14, e0215495 (2019).
pubmed: 31483836 pmcid: 6726224 doi: 10.1371/journal.pone.0215495
Rinschen, M. M. et al. VPS34-dependent control of apical membrane function of proximal tubule cells and nutrient recovery by the kidney. Sci. Signal 15, eabo7940 (2022).
pubmed: 36445937 pmcid: 10350314 doi: 10.1126/scisignal.abo7940
Pino, L. K. et al. The Skyline ecosystem: informatics for quantitative mass spectrometry proteomics. Mass Spectrom. Rev. 39, 229–244 (2020).
pubmed: 28691345 doi: 10.1002/mas.21540
Harris et al. Array programming with NumPy. Nature 585, 357–362 (2020).
pubmed: 32939066 pmcid: 7759461 doi: 10.1038/s41586-020-2649-2

Auteurs

Naziia Kurmasheva (N)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0002-9609-5811

Aida Said (A)

Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.

Boaz Wong (B)

Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Ottawa Hospital Research Insitute, Ottawa, ON, K1H 8L6, Canada.
ORCID: 0000-0001-9407-4315

Priscilla Kinderman (P)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
ORCID: 0000-0001-7919-9072

Xiaoying Han (X)

Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
ORCID: 0009-0005-9109-5651

Anna H F Rahimic (AHF)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Alena Kress (A)

Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
Faculty of Biological Sciences, Goethe University, 60438, Frankfurt am Main, Germany.
ORCID: 0000-0001-5793-6377

Madalina E Carter-Timofte (ME)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Emilia Holm (E)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Demi van der Horst (D)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Christoph F Kollmann (CF)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0001-5928-3808

Zhenlong Liu (Z)

Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.

Chen Wang (C)

Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.

Huy-Dung Hoang (HD)

Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.

Elina Kovalenko (E)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Maria Chrysopoulou (M)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0003-4502-5060

Krishna Sundar Twayana (KS)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Rasmus N Ottosen (RN)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.

Esben B Svenningsen (EB)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0001-5118-6499

Fabio Begnini (F)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.

Anders E Kiib (AE)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0002-2199-3801

Florian E H Kromm (FEH)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.

Hauke J Weiss (HJ)

School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.
ORCID: 0000-0002-8265-8644

Daniele Di Carlo (D)

Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.

Michela Muscolini (M)

Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.

Maureen Higgins (M)

Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.

Mirte van der Heijden (M)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.

Angelina Bardoul (A)

Cancer Axis, CHUM Research Centre, Montreal, Canada.
Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, Canada.
Institut du Cancer de Montréal, Montreal, QC, Canada.

Tong Tong (T)

Department of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.
Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.
DCCC Brain Tumor Center, Copenhagen University Hospital, Copenhagen, Denmark.
ORCID: 0000-0002-8776-3478

Attila Ozsvar (A)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.

Wen-Hsien Hou (WH)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Vivien R Schack (VR)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0002-1365-3938

Christian K Holm (CK)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0002-2655-3362

Yunan Zheng (Y)

Small Molecule Therapeutics & Platform Technologies, AbbVie Inc., 1 North Waukegon Road, North Chicago, IL, 60064, USA.

Melanie Ruzek (M)

AbbVie, Bioresearch Center, 100 Research Drive, Worcester, MA, 01608, USA.

Joanna Kalucka (J)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
ORCID: 0000-0003-4887-7672

Laureano de la Vega (L)

Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.
ORCID: 0000-0003-2707-7414

Walid A M Elgaher (WAM)

Department 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: 0000-0002-8766-4568

Anders R Korshoej (AR)

Department of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.
Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.
DCCC Brain Tumor Center, Copenhagen University Hospital, Copenhagen, Denmark.
ORCID: 0000-0003-4285-8171

Rongtuan Lin (R)

Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.

John Hiscott (J)

Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.

Thomas B Poulsen (TB)

Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
ORCID: 0000-0002-0763-9996

Luke A O'Neill (LA)

School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.
ORCID: 0000-0002-4333-2748

Dominic G Roy (DG)

Cancer Axis, CHUM Research Centre, Montreal, Canada.
Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, Canada.
Institut du Cancer de Montréal, Montreal, QC, Canada.
ORCID: 0000-0002-6044-0118

Markus M Rinschen (MM)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
III. Department of Medicine and Hamburg Center for Kidney Health, Hamburg, Germany.
Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark.
ORCID: 0000-0002-9252-1342

Nadine van Montfoort (N)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.

Jean-Simon Diallo (JS)

Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Ottawa Hospital Research Insitute, Ottawa, ON, K1H 8L6, Canada.
ORCID: 0000-0002-4862-2795

Henner F Farin (HF)

Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
German Cancer Consortium (DKTK), Frankfurt/Mainz partner site and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
ORCID: 0000-0003-1558-5366

Tommy Alain (T)

Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.
ORCID: 0000-0002-0396-9138

David Olagnier (D)

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark. olagnier@biomed.au.dk.
ORCID: 0000-0001-6912-0674

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Thérapeutique › Biothérapie › Thérapie virale de cancers › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Diacides carboxyliques › Succinates › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Virus › Virus oncolytiques › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteur-2 apparenté à NF-E2 › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › I-kappa B Kinase › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéine-1 de type kelch associée à ECH › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Virus › Virus à ARN › Virus à ARN de polarité négative › Mononegavirales › Rhabdoviridae › Vesiculovirus › Virus de la stomatite vésiculeuse de type Indiana › Octyl itaconate enhances VSVΔ51 oncolytic...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › Octyl itaconate enhances VSVΔ51 oncolytic...