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Oesophageal and Colorectal Cancer

Dr Joanne Lysaght
Dr. Joanne Lysaght, HRB Postdoctoral Fellow

Obesity has increased markedly over the past two decades and while numerous epidemiological studies have established a significant association between obesity and cancer, with obesity estimated to account for up to 20% of cancer deaths, the underlying mechanisms remain unclear. A state of low-grade chronic inflammation exists in obese individuals and this is thought to be a major contributing factor for the increased incidence of a range of cancers, including oesophageal and colorectal adenocarcinoma. Visceral adiposity, in particular, is a major risk factor for the development of inflammation, the metabolic syndrome and cancer. The majority of studies to date on obesity-associated inflammation have examined adipose tissue macrophages and their role in exacerbating this inflammation. However, more recent animal studies have pointed to T cells as key regulators in the initiation and maintenance of obesity-associated inflammation. However, the activation status and role of T cells in human visceral adipose tissue inflammation has not been examined to date.

The aim of this research project is to study adipose tissue from patients undergoing resective surgery for oesophageal and colorectal cancer, to investigate the mechanisms where obesity may contribute to the development and progression of these malignancies. Visceral abdominal fat has been identified as the essential fat depot for patho-genetic theories that relate obesity, metabolic syndrome and cancer. In a prospective study, subpopulations of immune cells, including T cells, in freshly digested, resected subcutaneous and omental adipose tissue are being characterised and analysed in order to determine how obesity status and cancer can affect innate and adaptive immune cells. Innate and adaptive immune cells are also being assessed in matched peripheral blood to determine how excess adipose tissue may regulate systemic immune responses, potentially affecting the anti-tumour immune response.

In a retrospective study, the activation status and localisation of distinct immune cells within the tumour microenvironment is being determined by immunohistochemistry using specifically generated tissue micro-arrays. IHC data is then be correlated with clinical parameters including BMI, visceral adiposity, metabolic syndrome status, pathological features and overall survival in order to examine the anti-tumour immune response in obese patients.

On completion of this project, which is currently funded by a HRB Fellowship award, it is anticipated that our knowledge of the regulatory mechanisms linking obesity, metabolic syndrome, immunomodulation and tumour growth will be greatly enhanced. It is hoped that potential immuno-therapeutic targets will be identified which could prevent or slow the progression of a number of obesity-associated pathologies including cancer.

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Last updated 23 November 2016 Surgery - Web Administrator (Email).