Project description
Targeting the tumour microenvironment for enhanced immunotherapy
The tumour microenvironment (TME) is a complex network of cells embedded in an altered extracellular matrix that surrounds and supports tumours. It plays a crucial role in cancer progression, often fostering an immunosuppressive environment that helps tumours evade immune detection and treatment. The ERC-funded EicoMet project aims to target tumour-associated macrophages (TAMs), one of the most abundant and immune-suppressive cell populations in the TME. To reprogramme TAMs from an immunosuppressive state, researchers will inhibit the enzyme HPGDS. This metabolic editing is expected to enhance immune cell infiltration in the tumour and overcome resistance to current treatments, offering new opportunities for combination therapies.
Objective
The field of cancer immunotherapy has witnessed exciting therapeutic advances in the last decade, but still a large fraction of patients is not responsive and several cancer types are refractory to this therapy. The presence of a strongly immunosuppressive environment is a likely explanation for the suboptimal efficacy of immunotherapy. One of the most abundant and immune suppressive population in the tumor microenvironment (TME) is represented by tumor-associated macrophages (TAMs). Therefore, several strategies that sculpt the TAM phenotype away from their immunosuppressive state are expected to become the next generation immunotherapies.
Supported by the ERC consolidator grant ImmunoFit, we recently unveiled that the metabolic editing of the TME via the pharmacological and genetic inhibition of HPGDS in macrophages (an enzyme involved in the production of prostaglandin D2 from arachidonic acid), represents a novel therapeutic strategy to sculpt TAMs away from their immunosuppressive state, increase infiltration and fitness of CD8+ T cells and NK cells, and promote tumor vessel normalization. This change in the TME upon HPGDS inhibition overcomes resistance to current immunotherapeutic regimens in melanoma and other cancer indications. This proposal aims to de-risk HPGDS targeting by delivering a lead compound with proven efficacy in several preclinical models. The deliverables of this project will open-up a window of opportunities in immune-oncology and lead to novel combination therapies by increasing the potency of the current therapeutic approaches.
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 clinical medicine oncology skin cancer melanoma
- medical and health sciences basic medicine immunology immunotherapy
- 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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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-POC - HORIZON ERC Proof of Concept Grants
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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-2023-POC
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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.
9052 ZWIJNAARDE - GENT
Belgium
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.