Jean-François Fonteneau Innovative strategies inducing immunogenic cancer cell death : application to mesothelioma treatments
Course and current status
Jean Francois Fonteneau was born in Montaigu, France, in 1971. He received the M.A. degree in cellular biology from Rennes University, Rennes, France, in 1994, and the Ph.D. degree from Nantes University, Nantes, France, in 1999. During his thesis training, he studied CD8+ T lymphocytes response against melanoma in the INSERM Laboratory of Pr Francine Jotereau. He then joined the 2011 Nobel prize Dr Ralph Steinman's Laboratory as a Postdoctoral Fellow under the direction of Dr Nina Bhardwaj at Rockefeller University, New York, NY, USA, from 2000 to 2003, where he studied dendritic cells biology, notably cross-presentation of viral antigens and interactions between virus/myeloid DC/plasmacytoid DC. In 2003, he returned to Pr Francine Jotereau Laboratory, INSERMU892, Nantes to identify new melanoma epitopes recognized by CD8+ and CD4+ T cells. In 2009, he joined Dr Marc Gregoire's Laboratory, INSERMU892, Nantes, to study immune response against pleural mesothelioma and innovative strategies to induce Immunogenic cell death of this cancer.
Scientific summary
Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura, usually associated with chronic asbestos exposure. Clinical strategies for MPM treatments including chemotherapy, radiotherapy and surgery, are of limited efficacy, urging search for new therapeutic approaches. Our laboratory is studying two new therapeutic strategies to treat this cancer, which are based on the induction of an immunogenic tumor cell death which may induce an anti-tumor immune response. These strategies are (1) the use of epigenetic drugs such as hypomethylating drugs and/or histone deacetylase inhibitors, and (2) the use of oncolytic virus, such as the vaccine attenuated strain of Measles virus, which kills specifically tumor cells. We study the immunological consequences of these treatments such as their effects on tumor associated antigen expression. We characterize the release of “damage associated molecular pattern” by tumor cells killed by these treatments and how it affects the maturation status of dendritic cells. We also study the immunogenic status of untreated MPM tumor cells such as their expression of tumor associated antigens and their recognition by T cells.
