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H2020Staff exchange2018–2022

DISCOVER · Death receptor signalling in tumour immune editing

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-01-01 → 2022-12-31
EU contribution
€904,500
Participants
9
Scheme
MSCA-RISE

Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.

Results in brief

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. Immune cells kill tumour cells using proteins, called death ligands, that they carry on their surface. These death ligands bind to so-called death receptors, often present on the surface of the cancer cells. This binding initiates a suicide programme in the cancer cell. As tumours evolve, this process becomes less effective, allowing the tumour cells to overgrow. The aim of the DISCOVER project is to bring a collaborative research network together to determine how exactly these proteins work and how their role evolves in tumour - immune cell interactions. The research programme is focused on an interdisciplinary area between immunology and cancer cell biology, which – despite its huge importance – is currently underexplored. The overarching aim of the DISCOVER programme is to address the role of the death ligand-death receptor signalling system across the three phases of tumour immune editing (elimination, equilibrium and escape). The aim will be addressed across three specific objectives: 1. Identify approaches to block death receptor-induced tumour cell invasion driving metastasis 2. Determine strategies to block tumour immune tolerance 3. Identify mechanisms to activate novel pathways of DR-mediated tumour cell death Overall, DISCOVER will have a strong potential to discover new targets for therapy and therapeutic lead molecules with commercial value, which will open new avenues of research and lead to follow-on work in this promising area.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • UNIVERSITY OF GALWAY · GalwayCoordinatorIreland
  • APOFAS BIOTECH · RennesCity levelFrance
  • CELL STRESS DISCOVERIES LIMITED · GalwayIreland
  • DOKUZ EYLUL UNIVERSITESI · Alsancak IzmirTürkiye
  • ENIOS APPLICATIONS IDIOTIKI KEFALAIOUCHIKI ETAIREIA · KALLITHEAGreece
  • INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisFrance
  • IZMIR BIYOTIP VE GENOM MERKEZI · İzmirTürkiye
  • SEQOME LIMITED · WaterfordIreland
  • UNIVERSITAET BERN · BernSwitzerland

Links

Data: CORDIS, © European Union