The immune system is a sophisticated biological mechanism that has evolved to distinguish between self and non-self. It eradicates tumour cells or cells infected with unwanted viruses using either cytolytic granules containing perforins and granzymes or ligands of the TNF superfamily such as FasL, TNF or TRAIL. The latter is of major interest in oncology because of its selectivity for tumour cells. Our team aims to understand how TRAIL signal transduction is regulated and to design new therapeutic approaches to treat cancer patients.