Title:Modulation of the Type I Interferon Response Defines the Sensitivity of Human Melanoma Cells to Oncolytic Measles Virus
Volume: 16
Issue: 6
Author(s): Ferdaous Allagui, Carole Achard, Clarisse Panterne, Chantal Combredet, Nathalie Labarrière, Brigitte Dréno, Amel Benammar Elgaaied, Daniel Pouliquen, Frédéric Tangy, Jean-François Fonteneau, Marc Grégoire and Nicolas Boisgerault
Affiliation:
Keywords:
Melanoma, Interferon, Measles virus, Oncolytic, Cancer virotherapy, Ruxolitinib.
Abstract: Background: Oncolytic viruses such as live-attenuated, vaccine strains of measles virus
(MV) have recently emerged as promising cancer treatments, having shown significant antitumor activity
against a large variety of human tumors.
Objective: Our study aims at determining which parameters define the sensitivity of human melanoma
cells to oncolytic MV infection.
Methods: We analyzed both in vitro and in vivo the oncolytic activity of MV against a panel of human
melanoma cell established in our laboratory. We tested whether either type I interferons or the interferon
pathway inhibitor Ruxolitinib could modulate the sensitivity of these cells to oncolytic MV infection.
Results: Human melanoma cells exhibit varying levels of sensitivity to MV infection in culture and as
tumor xenografts. As these differences are not explained by their expression level of the CD46 receptor,
we hypothesized that antiviral immune responses may be suppressed in certain cell resulting in their inability
to control infection efficiently. By analyzing the type I IFN response, we found that resistant
cells had a fully functional pathway that was activated upon MV infection. On the contrary, sensitive
cell showed defects in this pathway. When pre-treated with IFN-α and IFN-β, all but one of the sensitive
cell became resistant to MV. Cells resistant to MV were rendered sensitive to MV with Ruxolitinib.
Conclusion: Type I interferon response is the main determinant for the sensitivity or resistance of
melanoma to oncolytic MV infection. This will have to be taken into account for future clinical trials on
oncolytic MV.
