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 crosspresentation 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-a, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-a 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 þ 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-a, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response.

Radioimmunotherapy (RIT) is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue), and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 ((213)Bi) irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that (213)Bi-treated MC-38 cells release "danger signals" and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.