Treating Liver Metastasis

Introduction

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.

Clinical Need

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.

Challenges in Current Therapies

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 tumor control.

Hypothesis

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 dendritic cells (DCs).

Team Expertise

Our team brings together experts in the following areas:

• The biology of tissue-resident myeloid (Ginhoux, PI4) and lymphoid (Gasteiger, cPI) cells
• Liver immunology (Fumagalli, PI3)
• The development of novel immunotherapeutic strategies that modulate immune cells in the fight against cancer (Vivier, PI2)

Research Objectives

By combining cutting-edge single cell and spatial transcriptomics of human patient samples with cross-species analyses in advanced genetic mouse models, we aim to:

1. Identify cellular interactions defining the metastatic tumor microenvironment across murine and human tissue specimens.
2. Investigate immune cell functions regulating metastatic disease using a unique combination of advanced genetic mouse and human tissue models.
3. Harness the anti-tumoral functions of innate immune cells via next generation cell engagers.