Spatial multi-omics to explore immunometabolic heterogeneity in nonalcoholic steatohepatitis-related hepatocellular carcinoma
Lead Researcher: Dr Zoe Hall
Liver cancer is one of the leading causes of cancer-related deaths worldwide, with more than a million cases expected by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is a very complex form of cancer which makes the development of new therapies is challenging. Drugs which target the immune system and get it to attack the cancer cells in HCC are often successful. At the same time patients with HCC can also have fatty liver disease, where fats accumulate in the liver and affect the liver’s ability to function properly. However, the immune targeting drugs have limited success in patients with HCC and who also have fatty liver disease.
The liver is made of many different cell types, including immune cells. The immune cells may be protective and “search” for and removing tumour cells, but they may also cause inflammation and increase cancer risk. When the liver starts to have problems metabolising fats it can contribute to the development and progression of HCC. Fats can interfere with the liver’s immune cells, and this can affect their ability to find and kill the HCC cells.
In the past decade, new methods and technologies have been developed that can quantify DNA, RNA, proteins and chemicals in biological samples. In this project, we will use a combination of these new methods to measure levels of chemicals across different parts of tissues and cells. We will explore the how different fats are found in the tumour and how they are connected to different tumour cells. Using these technologies, we can build a “chemical signature” across the tumour, and between tumours from different patients, to understand better the link between the immune system and metabolism. From this signature we will decide the best treatment for patients and lead to design of novel drugs for HCC.