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Oncotarget. 2015 Dec 29;6(42):44892-904. doi: 10.18632/oncotarget.6285.

Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response.

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INSERM, UMR892, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
CNRS, UMR6299, Institut de Recherche en Santé de l'Université de Nantes, Nantes, France.
Université de Nantes, Nantes, France.
INSERM UMS016, SFR Santé, Nantes, France.
INSERM UMRS1087, Institut du Thorax, Nantes, France.
CNRS UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France.
CHU de Nantes, Service d'Oncologie Médicale Thoracique et Digestive, Nantes, France.
CHU de Nantes, Service de Pneumologie, Nantes, France.


Attenuated measles virus (MV) is currently being evaluated as an oncolytic virus in clinical trials and could represent a new therapeutic approach for malignant pleural mesothelioma (MPM). Herein, we screened the sensitivity to MV infection and replication of twenty-two human MPM cell lines and some healthy primary cells. We show that MV replicates in fifteen of the twenty-two MPM cell lines. Despite overexpression of CD46 by a majority of MPM cell lines compared to healthy cells, we found that the sensitivity to MV replication did not correlate with this overexpression. We then evaluated the antiviral type I interferon (IFN) responses of MPM cell lines and healthy cells. We found that healthy cells and the seven insensitive MPM cell lines developed a type I IFN response in presence of the virus, thereby inhibiting replication. In contrast, eleven of the fifteen sensitive MPM cell lines were unable to develop a complete type I IFN response in presence of MV. Finally, we show that addition of type I IFN onto MV sensitive tumor cell lines inhibits replication. These results demonstrate that defects in type I IFN response are frequent in MPM and that MV takes advantage of these defects to exert oncolytic activity.


measles virus; mesothelioma; oncolytic virotherapy; oncolytic virus; type I interferon

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