Oncolytic measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by human myeloid and plasmacytoid dendritic cells

Carole Achard 1 Jean-Baptiste Guillerme 1 Daniela Bruni 2 Nicolas Boisgerault 1 Chantal Combredet 2 Frédéric Tangy 2 Nolwenn Jouvenet 2 Marc Grégoire 1 Jean-François Fonteneau 1, *
* Auteur correspondant
1 CRCNA - Centre de Recherche en Cancérologie / Nantes - Angers
2 Génomique virale et vaccination
Abstract : Attenuated measles virus (MV) is currently being evaluated in clinical trials as an oncolytic therapeutic agent. Originally used for its lytic activity against tumor cells, it is now admitted that the effectiveness of MV also lies in its ability to initiate antitumor immune responses through the activation of dendritic cells (DCs). In this study, we investigated the capacity of oncolytic MV to convert human blood myeloid CD1cC DCs and plasmacytoid DCs (pDCs) into cytotoxic effectors. We found that MV induces the expression of the cytotoxic protein TNF-related apoptosis-inducing ligand (TRAIL) on the surface of DCs. We demonstrate that the secretion of interferon-a (IFN-a) by DCs in response to MV is responsible for this TRAIL expression. Several types of PRRs (pattern recognition receptors) have been implicated in MV genome recognition, including RLRs (RIG-I-like receptors) and TLRs (Toll-like receptors). We showed that CD1cC DCs secrete modest amounts of IFN-a and express TRAIL in an RLR-dependent manner upon exposure to MV. In pDCs, MV is recognized by RLRs and also by TLR7, leading to the secretion of high amounts of IFN-a and TRAIL expression. Finally, we showed that MV-stimulated DCs induce TRAILmediated cell death of Jurkat cells, confirming their acquisition of cytotoxic functions. Our results demonstrate that MV can activate cytotoxic myeloid CD1cC DCs and pDCs, which may participate to the antitumor immune response.
Keywords : oncolytic virus plasmacytoid dendritic cells type I interferon TRAIL Measles virus myeloid dendritic cells
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Article dans une revue
OncoImmunology, Taylor & Francis, 2016, 6 (1), pp.e1261240. 〈10.1080/2162402X.2016.1261240〉
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Carole Achard, Jean-Baptiste Guillerme, Daniela Bruni, Nicolas Boisgerault, Chantal Combredet, et al.. Oncolytic measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by human myeloid and plasmacytoid dendritic cells. OncoImmunology, Taylor & Francis, 2016, 6 (1), pp.e1261240. 〈10.1080/2162402X.2016.1261240〉. 〈inserm-01480165〉

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