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Measles virus-vaccine infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells
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Edité par CCSD ; American Association for Cancer Research -
International audience. Purpose: Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine (MV) is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells. Experimental design: Here, we investigated, in vitro, the effects of MV-infected tumor cells on phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to MV-infected or UV-irradiated tumor cells. Results: We found that only MV-infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of MV ssRNA with TLR7. We observed that MV-infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen, NYESO-1, to a specific CD8+ T-cell clone, when pDC were cocultured with MV-infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells. Conclusions: Altogether, our results suggest that the use of MV in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen presenting cells in the immune response.
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