Objective
Prostate cancer (PC) is the most common male cancer in the United Kingdom and more effective treatments are needed to control the lethal late-stage disease, termed castration-resistant PC (CRPC). CRPC is largely refractory to immunotherapeutic interventions mainly due to its tumour-immune microenvironment (TIME) with low infiltration of activated anti-tumour immune cells.
Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme which catalyses the transfer of methyl groups from S-adenosylmethionine to nicotinamide. Independent studies have implicated NNMT upregulation in sustaining aggressiveness of a specific subset of CRPC with stem cell-like features (CRPC-SCL), in several cellular and organoid models. We’ve recently described a “moonlighting” function of this enzyme, which can be secreted by cancer cells (extracellular NNMT – eNNMT) and activate TLR4-dependent NF-kB signalling in macrophages. Preliminary data demonstrate that PC secrete eNNMT, but how eNNMT may modulate the TIME, remains unknown.
This project aims to elucidate the role of eNNMT in shaping the TIME of CRPC-SCL. eNNMT release by CRPC-SCL murine cells and organoids, overexpressing NNMT will be quantified by ELISA. Using the state-of-the-art micro-mapping technology, we will identify eNNMT interactors in immune cells, to gain insight into the signalling pathways primed by eNNMT. Functional assays will be performed in co-cultures of CRPC-SCL models and immune cells, in the presence or absence of eNNMT blockage.
Defining eNNMT as a mediator of immune modulation in CRPC-SCL will provide mechanistic insights into tumour–immune crosstalk and establish the basis for novel immunotherapeutic strategies using eNNMT-neutralizing antibodies. Importantly, this project will also establish a pipeline to identify interactors of secreted factors/biomarkers with immune modulatory potential.
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.
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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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Topic(s)
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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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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-2025-PF
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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.
OX1 2JD Oxford
United Kingdom
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.