Christophe Caux, PhD

2007-2008 BCRF Project:
Co-Investigator: Jean-Yves Blay, MD, 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:
Christophe Caux received his PhD degree from Université Claude Bernard from Lyon, France, and has developed his scientific career since 1992 within the Laboratory for Immunological Research of Schering-Plough in Dardilly, France. He has been involved in numerous scientific observations on human dendritic cells (DC), sentinel of the immune system. In particular, his group has been a pioneer in i) in vitro DC expansion, ii) DC heterogeneity in development and function, iii) DC/T/B lymphocyte dialogue, iv) chemokines in DC trafficking, v) "Pathogen Recognition Receptor" such as Toll-Like-Receptors (TLR) in linking DC at the interface between innate and acquired immunity. These observations have been the basis for the definition of strategies to manipulate DC in vivo in order to reactivate anti-tumor immunity, and his contribution to the field is illustrated by over 80 original publications. He is an Editor of the Journal of Leucocyte Biology and is a member of several scientific organizations.

Since 2004 Dr Christophe Caux is research director within the INSERM unit "Oncogenesis and Tumor Progression" hosted in the anti-cancer centre Léon Bérard in Lyon, France. He is co-directing with Pr. Jean-Yves Blay, medical oncologist, the team "Cytokine and Cancer" that has a long history in tumor immunity. The team has in particular reported that in breast carcinoma the tumor environment impairs immune responses through alteration of DC development and functions. Furthermore, the group has long experience in developing and evaluating strategies of immune stimulation against tumors in mouse models. In the recent years, the team has investigated the role of the immunological status of the patients and its correlation with the outcome of cancer patients and the development of innovative clinical trials.

Dr. Caux's research interests with Jean-Yves Blay 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.