Objective
"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure acute myeloid leukemia (AML) via the immunological graft-versus-leukemia (GVL) effect, but relapse through immune evasion is frequent and accounts for 50% of the allo-HSCT-related mortality. The current strategy for relapse relies on chemo- or targeted therapy combined with donor lymphocyte infusions. Still, only few patients achieve long-term cure, underlining the urgent need for a better mechanistic understanding and more effective treatments.
Our recent work indicates that metabolic adaptations in AML—induced by prior chemotherapy exposure—act as protective ""shields"" against anti-leukemia immunity. Notably, we identified the bioactive lipids phosphatidic acid (PA) and oxylipins as two such shields. With LIFE, we will test the concept that selected bioactive lipids drive AML relapse—and that blocking them can enhance the GVL response and improve allo-HSCT outcomes.
We will integrate lipidomics for bioactive lipid detection, spatial and single-cell technologies, and functional genomics with in vivo allo-HSCT models and primary human AML samples to define the molecular effects of PA (Aim 1) and oxylipins (Aim 2) on immune evasion. Importantly, we will test how targeting these axes synergizes with donor immune cells and improves leukemia control. In parallel, we will use focused in vitro and in vivo CRISPRi screens to discover lipid pathway genes whose inhibition sensitizes AML to combined chemo-immune pressure (Aim 3).
This project will, for the first time, delineate how AML-derived bioactive lipids orchestrate immune evasion and provide a rationale for combinations targeting these pathways to improve allo-HSCT outcomes. Beyond allo-HSCT, we will uncover fundamental principles of how bioactive lipids shape tumor–immune interactions. By turning the metabolic shields into vulnerabilities, LIFE will deliver novel entry points for next-generation cancer therapies.
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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
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine transplantation
- medical and health sciences clinical medicine oncology leukemia
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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-ERC - HORIZON ERC 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-2026-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.
4051 Basel
Switzerland
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.