Jean-Yves Blay, MD, PhD

2007-2008 BCRF Project:
Co-Investigator: Christophe Caux, PhD, Cancéropôle Lyon Rhône-Alpes, INSERM, Hopital Edouard Herriot, Lyon, France

Through BCRF support since 2004, the French scientists have conducted a series of original scientific observations demonstrating that breast tumor cells subvert the immune system to their own advantage. Of importance, they have shown that tumor cells alter function in dendritic cells (the educating cells for the immune system) and mediate increase in regulatory T cell (immune suppressors) frequency, resulting in increased risk of breast cancer relapse.

In 2006-7, they made major progress. First, they demonstrated that within the breast tumor environment, TGFβ plays a central role in the functional alteration of plasmacytoid dendritic cells, favoring a state of immune tolerance. Second, they established that Treg are recruited within the tumor where their selective activation leads to dominant local immuno-suppression. Third, they obtained evidence that oncogenic transformation of mammary epithelial cells is associated with the acquisition of immune evasion properties. In 2007-2008 they will investigate the immunogenicity of different cell death pathways of tumor cells in vitro and in preclinical models with the goal of evaluating therapeutic strategies associated with drugs targeting tumor specific apoptosis and immune reactivation.

Mid-Year Progress Report:
The BCRF grants have allowed the French team to demonstrate that breast tumor cells subvert the immune system to their own advantage. Tumor cells alter dendritic cells (the educating cells for the immune system) function and mediate increase in regulatory T cell (immune suppressors) frequency, resulting in increased risk of breast cancer relapse. Through the 2006-7 and 2007-2008 BCRF grant, the researchers have made major progress.

First, they demonstrated that within the breast tumor environment, TGFβ play a central role in the functional alteration of plasmacytoid dendritic cells (PDC) favoring a state of immune tolerance. Second, they established that Treg are recruited within the tumor where their selective activation leads to dominant local immuno-suppression. Third, preliminary observations suggest that PDC and Treg cooperate to create a network dominated by immunosuppressive factors (TGFβ, IL10) leading to immune evasion. Finally, they have developed all the tools that will permit investigation of the immunogenicity of different cell death pathways of tumor cells, in vitro and in preclinical models with the aim to evaluate therapeutic strategies associating drugs targeting tumor specific apoptosis and immune reactivation.

Bio:
Dr. Jean-Yves Blay is Professor of Medicine at the Université Claude Bernard from Lyon, France, and the Scientific Director of the Canceropole Lyon Rhône Alpes, a network of more than 1500 researchers and physicians working in the field of cancer in the French Rhône-Alpes region. He is also vice chairman of the EORTC Translational Research Advisory Committee, member of the Protocol Review Committee of EORTC, and Vice-Chairman of the Soft Tissue and Bone Sarcoma group of EORTC. He is the National Representative for the European Society of Medical Oncology. He has been a reviewer for the Journal of Clinical Oncology, Blood, Cancer, Annals of Oncology, European Journal of Cancer, among others. Dr. Blay has published over 120 peer-reviewed articles, in addition to over 200 abstracts and book chapters.

His research interests focus on the biology of breast carcinoma and relation between tumor microenvironment and malignant cells with the goal of clinical applications in the fields of diagnosis, prognosis and treatment. He is also involved in clinical and biological research in the field of soft tissue sarcomas. Dr. Blay is an active member of the European Society of Medical Oncology, the American Society of Clinical Oncology, the American Association of Cancer Research and has served as member of Scientific Committees for the ESMO and AACR meetings. Dr Blay received his M.D. degree from the Université Claude Bernard in 1990. He performed Oncology and Internal Medicine training at Universite Lyon I and in the Institut Gustave Rousy in Paris. At the completion of his fellowship, he joined the staff of the Comprehensive Cancer Center Leon Berard in Lyon, where he became the head of the Cytokine and Cancer Unit within an INSERM research unit. He took the position of Head of Medical Oncology Unit in University Hospital in Lyon in 1999 and Scientific Director of Canceropole Lyon Rhône Alpes in 2004.