The role of the non-canonical death receptor signalling in cancer and immune cells

Fonte Standard Gras
Identifiant

Unité de recherche

SEFRI

Numéro de projet

23.00342

Titre du projet

The role of the non-canonical death receptor signalling in cancer and immune cells

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	Allemand	Français	Italien	Anglais
Résumé des résultats (Abstract)	-	-	-

Textes saisis

Catégorie	Texte
Résumé des résultats (Abstract) (Anglais)	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 apoptosisinducing 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 noncanonical 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.

Catégorie

Texte

Résumé des résultats (Abstract)
(Anglais)

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 apoptosisinducing 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 noncanonical 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.