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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.

Author information

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.

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.

KEYWORDS:

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

PMID:
26539644
PMCID:
PMC4792599
DOI:
10.18632/oncotarget.6285
[Indexed for MEDLINE]
Free PMC Article

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