Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing
In this study, we show that several microtubule-destabilizing agents used for decades for treatment of cancer and other diseases also sensitize cancer cells to oncolytic rhabdoviruses and improve therapeutic outcomes in resistant murine cancer models. Drug-induced microtubule destabilization leads to superior viral spread in cancer cells by disrupting type I IFN mRNA translation, leading to decreased IFN protein expression and secretion. Furthermore, microtubule-destabilizing agents specifically promote cancer cell death following stimulation by a subset of infection-induced cytokines, thereby increasing viral bystander effects. This study reveals a previously unappreciated role for microtubule structures in the regulation of the innate cellular antiviral response and demonstrates that unexpected combinations of approved chemotherapeutics and biological agents can lead to improved therapeutic outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Nature communications - 6(2015) vom: 30. März, Seite 6410 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arulanandam, Rozanne [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2016 Date Revised 22.12.2020 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/ncomms7410 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM247506516 |
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| 245 | 1 | 0 | |a Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing |
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| 520 | |a In this study, we show that several microtubule-destabilizing agents used for decades for treatment of cancer and other diseases also sensitize cancer cells to oncolytic rhabdoviruses and improve therapeutic outcomes in resistant murine cancer models. Drug-induced microtubule destabilization leads to superior viral spread in cancer cells by disrupting type I IFN mRNA translation, leading to decreased IFN protein expression and secretion. Furthermore, microtubule-destabilizing agents specifically promote cancer cell death following stimulation by a subset of infection-induced cytokines, thereby increasing viral bystander effects. This study reveals a previously unappreciated role for microtubule structures in the regulation of the innate cellular antiviral response and demonstrates that unexpected combinations of approved chemotherapeutics and biological agents can lead to improved therapeutic outcomes | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Krishnan, Ramya |e verfasserin |4 aut | |
| 700 | 1 | |a Karmacharya, Raunak |e verfasserin |4 aut | |
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