Project description
Metabolic insight into liver metastases
Cellular metabolism, the conversion of nutrients into energy and essential biomolecules, is fundamental to cell survival and function. Within the tumour microenvironment, nutrient availability shifts dramatically, forcing immune cells to alter their metabolism. Such adaptations may impair the anti-tumour activity of immune cells such as CD8+ T cells. This metabolic competition is evident in metastatic sites such as the liver. The ERC-funded SpaceMet project aims to elucidate how metabolic heterogeneity within liver metastases affects CD8+ T cell function. Researchers will use cutting-edge methodological approaches to map local nutrient variations and examine how they influence T cell infiltration and activity. Furthermore, the study will investigate how tumour genetics shape these metabolic niches and influence immune surveillance, ultimately seeking insights to improve therapeutic outcomes.
Objective
While immune-based therapies targeting CD8+ T cells have transformed melanoma treatment, many patients still show inconsistent responses between primary tumors and metastases, particularly in the liver. CD8+ T cells face unique barriers in liver metastases, hindering their infiltration and suppressing their function. Recent studies show that CD8+ T cells adapt their metabolism based on the nutrients available in the tumor environment, and this metabolic adjustment plays a key role in their ability to fight cancer. Liver metastases have traditionally been studied as uniform in CD8+ T cell activity and metabolism; however, our findings reveal that each metastasis creates a distinct metabolic environment that impacts CD8+ T cell infiltration and function. This challenges the conventional view and highlights the hidden heterogeneity driving resistance to immunotherapy. Building on this, the SpaceMet project will address the three following key objectives. (1) Identify the functional mechanisms by which metabolite heterogeneity impacts CD8+ T cell infiltration and function. We will investigate the metabolic heterogeneity revealed through spatial metabolomics in mouse liver metastases using an in vitro assay that simulates CD8+ T cell infiltration and interaction with tumor cells under specific liver-like nutrient conditions. (2) Investigate to which extent the genetic background and cell of origin determine the formation and composition of heterogeneous metabolic environments in the liver. This will involve performing spatial metabolomics and immune profiling of liver metastases from melanoma with different genetic profiles, as well as from other cancers. (3) Advance metabolism-targeted immunotherapy for liver metastases towards preclinical applications. To achieve this, we will employ humanized mouse models and liver metastasis patient biopsies. We anticipate that understanding these local interactions will pave the way to overcome immune resistance in liver metastasis.
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
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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)
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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)
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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.
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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.
HORIZON-ERC - HORIZON ERC Grants
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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) ERC-2025-STG
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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.
3000 LEUVEN
Belgium
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