Optimising prehabilitation exercise to enhance tumour outcomes in advanced oesophageal cancer

This project seeks to understand the mechanisms by which exercise training affects the fitness of patients receiving neoadjuvant chemotherapy for oesophageal cancer and how these fitness changes relate to the multi-organ and immune cell functions. The immune system is highly responsive and positively adapts to exercise training in several clinical populations, including patients with cancer. A single bout/episode of exercise results in the mobilisation of highly functional effector CD8+ T cells and NK-cells into the circulation, while regular exercise improves homeostatic functions, including in vitro tumour elimination. This improvement in systemic immunity mitigates the effects of immune dysfunction caused by common cancer risk factors, including ageing and obesity, and is likely responsible for the strong association between regular exercise training and improved patient-reported outcomes in cancer patients. Indeed, murine cancer models have shown that exercise reduces tumour burden by increasing the frequency of tumour-infiltrating lymphocytes (TILs). However, of the few studies assessing exercise and immune function in cancer patients, none have definitively shown that exercise increases TILs.

We have received funding from the World Cancer Research Fund to conduct a 4-year randomised clinical exercise trial in patients with locally advanced oesophageal cancer. Surgery is the standard of care for patients with locally advanced oesophageal cancer. Before surgery, patients receive ~8 weeks of neoadjuvant chemotherapy and 7-8 weeks of recovery. We have shown that low-intensity prehabilitation exercise training can maintain aerobic fitness while promoting an influx of TILs. The frequency of TILs was positively associated with changes in aerobic fitness, suggesting that more immune infiltrates will occur if we can increase fitness. This project will investigate whether a higher-intensity exercise program promotes enhanced clinical outcomes and improved multi-organ and immune cell function. 

The successful candidate will undertake a PhD based in the School of Biosciences under Prof Adam Frampton, Dr David Bartlett, Dr Nicola Annels and other academics within the Faculty of Health and Medical Sciences. You will have access to state-of-the-art clinical exercise physiology equipment and laboratory space to assess broad metabolic and immunological assessment of primary cells and cell lines using tools such as mass spectrometry, high-resolution respirometry, flow cytometry, and RT-PCR.

Applicants must have a first or upper second-class honours degree from the UK (or equivalent qualification from international Institutions) in a relevant subject area. This PhD would suit students with a background in clinical exercise sciences and a passion for bridging biological sciences with clinical outcomes. Specifically, the student should be interested in understanding how exercise benefits adults with cancer. This work seeks to understand the mechanisms by which exercise training affects the fitness of patients receiving neoadjuvant chemotherapy for oesophageal cancer and how these fitness changes relate to the multi-organ and immune cell functions. 

Open to candidates who pay UK/home rate fees. See UKCISA for further information.

You will need to meet the minimum entry requirements for our PhD programme.