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Eileen will investigate the expression of genetic instability and how it shapes the immune microenvironment of oesophageal cancers.

Eileen Parkes of the Department of Oncology has been awarded the prestigious Wellcome Clinical Research Career Development Fellowship, a highly competitive scheme that enables healthcare researchers to take their work to the next level in patient benefit.

Eileen’s area of cancer research focuses on the interaction between genetic instability (a hallmark of cancer) and the impact it can have on the immune microenvironment of resulting cancer.

Understanding the immune microenvironment of cancer is very important, as tumours are known to establish immunosuppressive environments to support their growth and spread across the body. Further research into what genetic and immune system aspects influence this microenvironment will help us to develop new treatments to promote a tumour-suppressive environment and improve overall outcomes for patients.

Using this new funding from the Wellcome Trust, Eileen will be looking at oesophageal adenocarcinomas (OAC), a cancer of unmet need that shows high rates of genetic instability. Her focus will be on finding new genetic targets that are influencing the immune-suppressive microenvironment of OAC, in order to develop potential new treatments.

Specifically Eileen will look at chromosomal instability of OAC tumours and how this activates specific pathways, known as the cGAS-STING pathway, to ultimately reduce the stimulation of immune cells within the microenvironment.

STING (also known as Stimulator of interferon genes) play an important role in innate immunity. The STING pathway is responsible for inducing interferon production (signalling proteins used to alert other cells to an infection) when cells are infected by pathogens. Activation of these genes is thought to have great potential in enhancing anti-tumour immunity as well.

 

Cancer cells often have tangled, knotted DNA – this helps cancers grow, spread and resist anticancer treatments. One way cancers with tangled DNA do this is by preventing immune attacks by telling nearby normal cells, called fibroblasts, to make immune-inactivating proteins. 

My work suggests that one particular protein on fibroblasts protects cancers from immune cell attack. Understanding exactly how cancer cells tell fibroblasts to make this protein and what the consequences are for immune cells within the cancer is important because it could help us find new ways to attack these difficult-to-treat cancers.
- Dr Eileen Parkes