Human preclinical models of liver cancer to identify next generation therapeutic approaches to target tumour associated macrophages

This research project was awarded the 2024 Birmingham BRC Collaboration Fund

Status: Project complete

Liver cancer, also known as hepatocellular carcinoma (HCC), often develops in patients with chronic liver disease. This disease causes inflammation and scarring, which can lead to cancer. Survival rates for HCC remain poor, highlighting the need for new and more effective treatments.

A key player in this process is a type of immune cell called tumour associated macrophages (TAMs). While some macrophages can help the body fight cancer, others can promote tumour growth and limit the effectiveness of immunotherapy. Previous studies have suggested that the physical environment, including tissue stiffness, can influence how these cells behave.

Project aims

This project aimed to understand how the physical environment of the liver affects these cells and to find new ways to target them for therapy.

Using cutting-edge spatial transcriptomic and proteomic technologies, researchers have been able to study individual cells within human liver cancer tissue while preserving information about their precise location. The project has established new workflows at the University of Birmingham for selecting, preparing and analysing high-quality tissue samples using these advanced technologies. These methods have since been adopted by other research groups, extending the project’s impact.

A key achievement has been the optimisation of techniques used to accurately identify and map different cell populations within complex tumour tissues. This has enabled researchers to better characterise macrophages and other immune cells, understand how they are distributed throughout the tumour and surrounding tissue, and examine how they interact with important structural proteins and other components of the tumour microenvironment.

The project has also generated valuable datasets that will be integrated with laboratory-based three-dimensional models of liver disease. Together, these approaches will help researchers identify biological pathways involved in tumour development and progression, and prioritise potential targets for future macrophage-based therapies.