Project description
Understanding immune surveillance in cancer
Immune surveillance is the immune system's ability to trigger cell death in abnormal cells early during cancer development. This is facilitated by the TRAIL death ligand and its receptors DR4 and DR5. However, cancer cells can evade this by altering the signalling downstream from pro-apoptotic to pro-survival. Funded by the Marie Skłodowska-Curie Actions, the CHIRON project aims to fill the knowledge gaps in this pathway. Apart from a mechanistic understanding of the pathway's role in immune cells and cancer, researchers aim to develop small molecule inhibitors to block the DR-signalling pathway. Project findings are expected to guide the development of future tools for diagnosis and therapy.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2022-SE-01
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35340 İzmir
Türkiye
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