DISCOVER · Death receptor signalling in tumour immune editing

During tumour development there is a bi-directional communication between cancer cells and immune cells; the process termed tumour immune editing. The impact is reciprocal, shaping both the visibility and susceptibility of the tumour to immune eradication as well as the ability of the immune effector cells to recognise and launch an immune response against tumour cells. Death ligand-death receptor signalling is a key mechanism to kill tumour cells during the early stages of tumour development (tumour immune surveillance). However, the role of this signalling pathway in evolved tumours is poorly understood. Recent pioneering results from DISCOVER consortium members highlighted non-canonical signal tranduction pathways mediated by death receptors, which regulates both tumour cell behaviour (motility, invasion) and effector immune cell function in the tumour microenvironment. The aim of the DISCOVER proposal is to bring a collaborative research network together to determine the role of death ligand-death receptor signalling in tumour - immune cell interactions. The DISCOVER programme will determine how non-canonical signal transduction pathways driven by death receptors control effector immnue cell functions and tumour cell behaviour. The outputs of the research will be used to develop informed therapeutic strategies to interfere with non-canonical death receptor signalling in order to re-activate anti-tumour immune attack and sensitise tumour cells to this attack.The DISCOVER proposal will integrate the research activity of seven beneficiary organisations from 5 European countries, including 3 companies and create a framework for knowledge and reagent exchange for early stage and experienced researchers. The consortium will bring together scientists from immunology and cancer cell biology and combines these with expertise in systems biology, drug discovery and pre-clinical drug development thus forging a consortium where scientific discoveries drive innovation.