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.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC-SYG - HORIZON ERC Synergy GrantsHost institution
97070 Wuerzburg
Germany