Centre de Recherche en Cancérologie Nantes-Angers, France
Marc Grégoire obtained his PhD degree in Paris VI University in 1984. He was appointed INSERM full researcher in 1987, in Nantes, France. In 2000, he leads a research team (http://www.univ-nantes.fr/crcna/team4) whose field is mainly devoted to the study of innovative therapies to pleural mesothelioma. His team focuses the role of Measles virus vaccines (MV) to induce immunogenic cell death by apoptosis. His team, in collaboration with Dr. F. Tangy from Pasteur Institute (Paris, France) demonstrated that the MV infection of the tumor cells is specific, induces expression of danger signals by the infected dead cells, and favor activation of the antigen presenting cells such as the dendritic cells. This antitumor virotherapy is in progress to be proposed as an innovative strategy to treat aggressive cancers.
Dendritic Cells (DC) are antigen presenting cells specialized in inducing immune responses. Measles Virus vaccine (MV) was recently proposed as anti-tumor agent to target and kill specifically tumor cells, without infecting healthy cells. We demonstrated that myeloid dendritic cells (mDC) co-cultured with MV infected tumor cells, actively matured and cross-presented tumor antigen. Recently, we also investigated the effects of MV tumor infected cells on phenotype and functions of plasmacytoid DC. We studied maturation, cytokine production and tumor antigen cross-presentation by mDC and pDC exposed either to the virus alone, MV infected or UV irradiated tumor cells. We found that MV infected cells induce DC maturation with a strong cytokine production, notably IFN-α, whereas UV irradiated tumor cells and the MV alone did not. We also observed that MV infected and UV irradiated cells were similarly phagocytosed by DC, although this up-take was less important than in myeloïd DC. Interestingly, we observed cross-presentation of tumor antigen to a specific CD8+ T cell clone only when DC are co-cultured with MV infected tumor cells. Altogether, our results suggest that the use of MV, as anti-tumor virotherapy, may induce immunogenic tumor cell death allowing DC to cross-present tumor antigen. Data will be presented with effects on mesothelioma, melanoma and lung cancer.