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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Host-Pathogen Interactions
  • Humans
  • Interferon Type I / immunology
  • Interferon Type I / metabolism*
  • Measles virus / growth & development*
  • Measles virus / immunology
  • Measles virus / metabolism
  • Membrane Cofactor Protein / metabolism
  • Mesothelioma / immunology
  • Mesothelioma / metabolism
  • Mesothelioma / therapy*
  • Mesothelioma / virology
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / growth & development*
  • Oncolytic Viruses / immunology
  • Oncolytic Viruses / metabolism
  • Pleural Neoplasms / immunology
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / therapy*
  • Pleural Neoplasms / virology
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Time Factors
  • Virus Replication*


  • Antigens, CD
  • CD46 protein, human
  • Cell Adhesion Molecules
  • Interferon Type I
  • Membrane Cofactor Protein
  • Receptors, Cell Surface
  • nectin4 protein, human
  • Signaling Lymphocytic Activation Molecule Family Member 1