Project description
Oncometabolite dynamics for advanced dendritic cell tumour therapy
Immunotherapy harnesses the body’s immune system to fight cancer, highlighting the role of the tumour microenvironment (TME) in shaping immune responses. Manipulating tumour-derived metabolites, known as oncometabolites, may strengthen anti-tumour immunity. Research shows that deleting the aryl hydrocarbon receptor (AhR) in antigen-presenting cells can trigger tumour rejection, suggesting that AhR senses the composition of the TME and regulates immune activity. The ERC-funded REACT-DC project aims to identify metabolites in the TME that activate AhR and investigate their role in tumour rejection. It will also develop strategies to inhibit AhR or its downstream pathways in selected antigen-presenting cells using single-cell analysis, gene editing and computational chemistry, aiming to uncover therapeutic targets and prevent tumour escape.
Objective
"Owing to an increased appreciation of the potential for immunotherapy in neoplasia, much attention has been focuing on a greater understanding of the immune, bidirectional intricacies involving the Tumor MicroEnvironment (TME). Recent work has demonstrated that TME elicits environmental changes, metabolic in nature, in the host’s immune cells, that dampen their ability to REACT against tumors. Manipulating the biology of oncometabolites can strengthen an antitumor immune response as well as circumvent therapy resistance. Here I propose innovative modalities to tackle this problem. The Aryl hydrocarbon Receptor (AhR), best known as the receptor for dioxins, has recently been shown to be one ""central node"" for communication between host's cells and its ligands, disparate as the nature and source. I have recently found that selective AhR deletion in a subset of antigen presenting cells triggers the rejection of an otherwise progressive fibrosarcoma tumor in vivo. I thus hypothesize that, AhR, expressed in orchestrators of immune responsiveness, represents a key sensor of TME composition, influencing the outcome of an immune reaction against tumors. The main objective of this project is to identify AhR-activating metabolites in TME and disclose their impact on tumor rejection or progression. In parallel, I aim at developing novel advanced strategies, with a high degree of translatability to human cells, to specifically inhibit AhR or AhR-dependent programs in selected APCs. I will combine state-of-the-art technology with new and powerful technologies, including advanced single-cell analysis, promoter gene-editing approaches and computational chemistry. The potential of such a project is very high, because such metabolites may be predictors of immune activation or suppression in TME, and the downstream targets of those immunesuppressive oncometabiltes may represent druggable targets to inhibit tumor escape mechanisms."
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.
- natural sciences chemical sciences organic chemistry hydrocarbons
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences basic medicine immunology immunotherapy
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
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.
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.
Funding Scheme
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.
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
06123 Perugia
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.