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Treating Liver Metastasis

Project description

Investigating liver metastasis to improve immunotherapy

Liver metastases are common in various cancers. While new therapies aimed at enhancing T cell responses have shown promise, only a minority of patients benefit. Identifying new cells and molecules is crucial for developing next-generation immunotherapies. Targeting innate immune responses offers new opportunities for tumour control. The EU-funded TREATLIVMETS project aims to advance immunotherapy for liver metastases by studying the biology of innate lymphoid cells (ILCs) and myeloid cells. The project will use advanced genetic mouse models and human tissue samples to identify cellular interactions that define the metastatic tumour microenvironment, investigate immune cell functions that regulate metastatic disease, and harness the anti-tumoral properties of innate immune cells.

Objective

Liver metastases commonly develop in up to 50% of patients with various cancer types. The most common cancer that metastasizes to the liver is colorectal cancer (CRC). At least 25% of CRC patients develop colorectal liver metastases (CRLM) during their illness. CRLM represent the major unmet clinical need for this malignancy, as the 5-year survival rate of patients with unresectable disease does not exceed 2%. New therapies that promote antitumor immunity have been recently developed, mostly focusing on enhancing T cell responses. Although these therapies have led to unprecedented successes, only a minority of patients benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in next generation immunotherapies. Given the crucial role of innate immune responses in immunity, targeting these responses opens up new possibilities for tumour control. We hypothesize that the immunotherapy of liver metastases can be significantly improved through harnessing the biology of innate lymphoid cells (ILC), such as Natural Killer (NK) cells and ILC1s, and myeloid cells such as macrophages and DCs.

Our team brings together experts in the biology of tissue-resident myeloid (Ginhoux, PI4) and lymphoid (Gasteiger, cPI) cells, in liver immunology (Fumagalli, PI3), and in the development of novel immunotherapeutic strategies that modulate immune cells in the fight against cancer (Vivier, PI2). By combining cutting-edge single cell and spatial transcriptomics of human patient samples with cross-species analyses in advanced genetic mouse models, we aim
(1) to identify cellular interactions defining the metastatic tumor microenvironment across murine and human tissue-specimens,
(2) to investigate immune cell functions regulating metastatic disease using a unique combination of advanced genetic mouse and human tissue models, and
(3) to harness the anti-tumoral functions of innate immune cells via next generation cell engagers.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-SyG

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Host institution

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Net EU contribution

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.

€ 2 499 154,25
Address
SANDERRING 2
97070 Wuerzburg
Germany

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Region
Bayern Unterfranken Würzburg, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost

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.

€ 2 499 154,25

Beneficiaries (6)

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