title: Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response.
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.
authors.affiliation: 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.
authors.forename: Carole
authors.initials: C
authors.lastname: Achard
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boisgerault
authors.affiliation: 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.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Delaunay
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Roulois
authors.affiliation: Université de Nantes, Nantes, France.|INSERM UMS016, SFR Santé, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Nedellec
authors.affiliation: Université de Nantes, Nantes, France.|INSERM UMRS1087, Institut du Thorax, Nantes, France.
authors.forename: Pierre-Joseph
authors.initials: PJ
authors.lastname: Royer
authors.affiliation: Université de Nantes, Nantes, France.|INSERM UMRS1087, Institut du Thorax, Nantes, France.
authors.forename: Mallory
authors.initials: M
authors.lastname: Pain
authors.affiliation: CNRS UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Combredet
authors.affiliation: CNRS UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France.
authors.forename: Mariana
authors.initials: M
authors.lastname: Mesel-Lemoine
authors.affiliation: CHU de Nantes, Service d'Oncologie Médicale Thoracique et Digestive, Nantes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cellerin
authors.affiliation: Université de Nantes, Nantes, France.|INSERM UMRS1087, Institut du Thorax, Nantes, France.|CHU de Nantes, Service de Pneumologie, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
authors.affiliation: CNRS UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Grégoire
authors.affiliation: 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.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fonteneau
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008459:Measles virus / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D051916:Membrane Cofactor Protein / Q000378:metabolism; D008654:Mesothelioma / Q000276:immunology / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D010997:Pleural Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013997:Time Factors; D014779:Virus Replication; D000075983:Nectins
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007370:Interferon Type I; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C497857:CD46 protein, human; C442228:NECTIN4 protein, human; D000075983:Nectins
keywords: measles virus; mesothelioma; oncolytic virotherapy; oncolytic virus; type I interferon