Death receptor-ligand systems in tumourigenesis and cancer treatment

Based on recent studies from the Walczak laboratory (von Karstedt et al., Cancer Cell 2015; Hartwig et al., Molecular Cell, in press) and unpublished preliminary results recently obtained by the Walczak Lab, it has become apparent that, depending on the type of cancer and the oncogenic mutations driving them, different death receptor-ligand systems can support the in vivo progression of particular cancers. However, the mechanisms by which this is achieved are not well understood. In the present project we aim to unravel these mechanisms and to determine the therapeutic potential of perturbation of specific death receptor-ligand systems as possible new treatments for various types of epithelial cancers. We will define the contributions of death receptors and ligands expressed on tumour versus host cells in shaping a pro-tumourigenic microenvironment and evaluate the effect of perturbation of specific death receptor-ligand systems on growth and migratory capacity of cancer cells as well as on enhancing the efficacy of cancer immunotherapies, in particular those based on immune checkpoint blockade.