Oncotarget

Research Papers:

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

Carole Achard, Nicolas Boisgerault, Tiphaine Delaunay, David Roulois, Steven Nedellec, Pierre-Joseph Royer, Mallory Pain, Chantal Combredet, Mariana Mesel-Lemoine, Laurent Cellerin, Antoine Magnan, Frédéric Tangy, Marc Grégoire and Jean-François Fonteneau _

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Oncotarget. 2015; 6:44892-44904. https://doi.org/10.18632/oncotarget.6285

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Abstract

Carole Achard1,2,3, Nicolas Boisgerault1,2,3, Tiphaine Delaunay1,2,3, David Roulois1,2,3, Steven Nedellec3,4, Pierre-Joseph Royer3,5, Mallory Pain3,5, Chantal Combredet6, Mariana Mesel-Lemoine6, Laurent Cellerin7, Antoine Magnan3,5,8, Frédéric Tangy6, Marc Grégoire1,2,3 and Jean-François Fonteneau1,2,3

1 INSERM, UMR892, Institut de Recherche en Santé de l’Université de Nantes, Nantes, France

2 CNRS, UMR6299, Institut de Recherche en Santé de l’Université de Nantes, Nantes, France

3 Université de Nantes, Nantes, France

4 INSERM UMS016, SFR Santé, Nantes, France

5 INSERM UMRS1087, Institut du Thorax, Nantes, France

6 CNRS UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France

7 CHU de Nantes, Service d’Oncologie Médicale Thoracique et Digestive, Nantes, France

8 CHU de Nantes, Service de Pneumologie, Nantes, France

Correspondence to:

Jean-François Fonteneau, email:

Keywords: oncolytic virus, measles virus, oncolytic virotherapy, mesothelioma, type I interferon

Received: October 08, 2015 Accepted: October 22, 2015 Published: November 02, 2015

Abstract

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.


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