Dr Oliver Pearce
Tell us about the challenges you are tackling.
The extracellular matrix — the network of proteins that surrounds cells — has a major influence on how tumours develop and how the immune system responds to them.
In some cancers, the matrix forms a dense barrier that makes it difficult for immune cells to enter the tumour and recognise cancer cells. This can limit the effectiveness of potentially valuable immunotherapies, which rely on supporting the immune system to identify and destroy cancer cells.
Our lab is particularly interested in pancreatic and breast cancers, where the matrix is often especially dense and difficult for immune cells to penetrate.
How will you address these challenges with the new grant?
The extracellular matrix is incredibly complex. This grant will help us untangle that complexity and understand how specific components of the matrix regulate interactions between tumours and the immune system.
We suspect that the location of different features within the matrix may be more important than how abundant they are overall. To explore this, we will use spatial analysis approaches that allow us to map changes within tumours while combining multiple types of data — including genes, proteins and chemical modifications to proteins.
We will test how these changes affect tumour and immune cell behaviour using tumour models that we grow in the lab. These models recreate key features of the tumour environment, including the extracellular matrix, immune cells and blood vessels.
How could this work benefit patients?
Ultimately, we hope to develop treatments that alter the tumour environment in ways that allow immune cells to enter the tumour more easily and recognise cancer cells. These approaches could be used alongside immunotherapies to improve how well they work.
By the end of the six-year programme, we hope to have several potential treatments that we are testing in preclinical studies. We have already identified a small number of promising candidates that we are actively investigating in the lab.
We are also collaborating with several biotechnology partners. For example, with Neobe Therapeutics we are exploring the use of microorganisms to deliver enzymes that modify the tumour extracellular matrix. In addition, with Anomer Bio, we are studying small molecules that alter chemical modifications on proteins within the extracellular matrix, which may have important effects on how the immune system responds to tumours.