Projet CHIRON (Horizon Europe, appel à projets 2022)
Action : Staff Exchanges
Panel : Life Sciences
Statut du projet : SIGNED

Immune surveillance refers to the ability of the immune system to efficiently induce cell death (apoptosis) in aberrant cells during the early stages of tumour development. This induction of cell death involves the binding of the death ligand TRAIL (TNF-related apoptosis-inducing ligand) to its death receptors (DRs) DR4 and DR5 on the target cell. However, tumour cells can escape this immune surveillance by switching the signalling downstream of DRs from the canonical pro-apoptotic signal towards a survival signal. Previous work from CHIRON partners highlights that this non-canonical DR-signalling regulates both tumour cell behaviour and immune cell functions, demonstrating its central role in understanding the tumour microenvironment. Yet, many aspects of the DR-signalling pathways remain unresolved, hampering the exploitation for diagnostic and therapeutic purposes. CHIRON will address these gaps via its main scientific aims: (i) to develop novel small molecule inhibitors (SMIs) to inhibit non-canonical DR-signalling (WP1), (ii) to identify new DR4- and DR5-binding partners within tumour and immune cells (WP2), and (iii) to gain a mechanistic understanding of the role of the non-canonical DR-signalling pathway in immune cells and cancer types (WP3). To achieve this, the CHIRON consortium combines the multidisciplinary and complementary expertise and resources of six academic and three private sector partners to (i) generate novel knowledge and innovative tools, (ii) strengthen an efficient network of knowledge exchange for further innovative synergies, and (iii) develop the expertise of early-stage and experienced researchers through excellent training. The outputs of the research will (i) develop novel tools to sensitise tumour cells for TRAIL-induced cell death, (ii) guide future diagnostic and therapeutic strategies to utilize and modulate DR-signalling, and (iii) train the expertise necessary to turn such knowledge into innovative services and products.

Mots clés : trail, death receptors, dr4, dr5

Participants :
- Institut national de la santé et de la recherche médicale (France) — Partner, beneficiary, Recherche, subvention : 202400.0 €
- Izmir biyotip ve genom merkezi (Turquie) — Coordinator, beneficiary, Recherche, subvention : 202400.0 €
- Enios applications idiotiki kefalaiouchiki etaireia (Grèce) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 202400.0 €
- Anyo labs ab (Suède) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 165600.0 €
- Covalab (France) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 174800.0 €
- Université du 9 Septembre (Turquie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 202400.0 €
- Université nationale d'Irlande à Galway (Irlande) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 202400.0 €
- Université de Berne (Suisse) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université polytechnique et économique de Budapest (Hongrie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 179400.0 €
- Université de Bourgogne (France) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €