Department of Dermatology
Geneva University Hospital
24 rue Micheli-du-Crest
1211 Geneva 14/Switzerland
and
Louis-Jeantet Skin Cancer Lab 5.222
Geneva University Medical Center (CMU)
1, rue Michel Servet
1211 Genève 4/ Switzerland

Tel: ++41 22 372 9455 or ++ 41 22 372 3311 and ask for bip 857 782
Fax: ++41 22 702 5802
E-mail: Lars.French@medecine.unige.ch

Our laboratory performs translational research focused mainly on the tumor necrosis family (TNF) and aimed at identifying novel therapeutic approaches for severe skin diseases.

Dysregulation of apoptosis is involved in life-threatening pathologies that affect the skin, such as toxic epidermal necrolysis (TEN) and graft versus host disease (GVHD). We are currently trying to improve our understanding of the molecular mechanisms leading to death-receptor mediated apoptosis in these 2 diseases. Preclinical and early clinical results indicate that modulation of the function of pro-apoptotic molecules of the TNF family (Fas) have therapeutic potential. Such approaches, notably using novel recombinant inhibitors of Fas signaling, are being developped and tested in appropriate in vivo models of disease.

Immunotherapy represents a challenging treatment for skin cancers such as melanoma. Despite an apparent continuous growth, tumor cells are not ignored and tumor antigens are seen by immune cells in draining lymph nodes. Occasionally, this spontaneous antigen presentation leads to the induction of immunity and tumor regression, but in general tumor growth is associated with a state of immune tolerance. We are currently studying in detail the spontaneous immune reponses that occur against melanoma in an attempt to try to better understand what regulates the balance between immunogenicity and tolerogenicity to melanoma cells. A mouse melanoma model that better reflects the human pathology is currently being developped. The ultimate aim of the above studies is to define strategies by which to “boost “ spontaneous tumor immune responses in order to convert them into protective responses. Our current strategy is based on the injection of immunostimulatory molecules (targeting Dendritic Cells and T lymphocytes) into tumor-draining lymph nodes.

Selected publications :

Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat JH, Tschopp J, French LE. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 282:490, 1998

Huard B, Karlsson L. KIR expression on self-reactive CD8+ T cells is controlled by T-cell receptor engagement. Nature 403:325, 2000

Huard B, Schneider P, Mauri D, Tschopp J, French LE. T cell costimulation by the TNF ligand BAFF. J Immunol. 167:6225, 2001

French LE, Tschopp J. Protein-based therapeutic approaches targeting death receptors. Cell Death Differ. 10:117, 2003

Viard-Leveugle I, Bullani R, Meda P, Limat A, Saurat JH, Tschopp J, French LE . Intracellular Localization of Keratinocyte Fas Ligand Explains Lack of Cytolytic Activity of Resting Keratinocytes. J Biol Chem 278, 16183, 2003

Collaborators :

Bertrand Huard, PhD

Emmanuel Conatssot, PhD

Olivier Preynat-Seauve, PhD

Isabelle Viard-Leveugle, PhD

Olivier Gaide, MD/PhD

Prisca Schuler, biologist

Stéphanie Roques, biologist

Isabelle Leite, biology student

Gertraud Radlgruber, technician

Kerstin Grosdemange, technician

Karine Bosshard, technician