Meet our Expert: Sophie Acton

What questions are your lab trying to answer right now?  

Since immune cells can recognise and target cancer cells, our goal is to understand ways to recruit and support more immune cells into tumours. Our previous work has been to study how immune responses are regulated by the stromal cells (support cells) within lymph nodes, but we are now applying this knowledge to understand how the same interactions might be occurring within tumours. Our latest projects aim to understand how tertiary lymphoid structures (TLS) form, and to ask what immune functions that these structures support. TLS are aggregates of immune cells that develop in tissues which are chronically inflamed – in autoimmune disease and in some cancers.  We had discovered that some types of fibroblasts are able to support immune cell function within tumours, in similar ways to their interactions within lymph nodes. We are now working to understand how these immunoregulatory fibroblasts develop in inflamed tissues and what signalling crosstalk mechanisms they provide to the immune cells that they recruit and cluster with. 

What experimental approaches do you use for your research?  

We use models of cancer in mice, and cell lines in vitro to study how fibroblasts and immune cell communicate and respond to inflammatory signals. We use a wide range of techniques including microscopy, transcriptomics, flow cytometry and biochemistry assays for different aspects of the projects   

Why is the relationship between immune cells and support cells in lymph nodes important?   

The stromal cells in lymph nodes provide control and organisation to immune responses. They provide physical structures to guide immune cell migration and chemical cues to segregate different types of immune cells into different areas of the tissue. These stromal cells are also producing important growth factors, survival factors, and regulatory signals to ensure a coordinated and efficient immune response. Also, importantly, we have reported a mechanical crosstalk mechanism between immune cells and stromal cells which controls how the lymph node grows and expands (swollen glands) during an immune reaction.   

How might this relationship change in diseases like cancer?  

In the lymph node, we have found that a nearby tumour can quickly change the function of these important fibroblasts. The lymph node fibroblasts become more contractile, change the way they lay down matrix components like collagen molecules, and can ‘forget’ their functions in controlling and supporting immune cells around them. We would like to understand how these changes occur, and potentially find ways to block changes to lymph nodes to preserve immune function while fighting cancer cells nearby. 

Why is the lymph node a good model for studying immune cell interactions in tumours?  

We had discovered that some types of fibroblasts are able to support immune cell function within tumours, in similar ways to their interactions within lymph nodes. We are now working to understand how these immunoregulatory fibroblasts develop in inflamed tissues and what signalling crosstalk mechanisms they provide to the immune cells that they recruit and cluster with.   

Are there any promising therapies you're excited about?  

If we can unpick key signals which control the behaviour of fibroblasts, either in lymph nodes, or in tumours, then it would open up a new avenue for therapeutic interventions that could increase immune cells activity in tumours. I would hope that this would lead to more patients responding to immunotherapy and entering remission. 

Further Information: 

• UCL Laboratory for Molecular Cell Biology
• Staff profile: Sophie Acton