Measles Virus Vaccine-Infected Tumor Cells Induce Tumor Antigen Cross-Presentation by Human Plasmacytoid Dendritic Cells

Purpose: Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine 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 measles virus vaccine-infected tumor cells on the phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to measles virus vaccine-infected or UV-irradiated tumor cells. Results: We found that only measles virus vaccine-infected cells induced pDC maturation with a strong production of IFN-alpha, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-alpha production was triggered by the interaction of measles virus vaccine single-stranded RNA (ssRNA) with TLR7. We observed that measles virus vaccine-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 measles virus vaccine-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 measles virus vaccine in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-alpha, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response. Clin Cancer Res; 19(5); 1147-58. (C) 2012 AACR.