“Oesophageal cancer is a devastating disease, and even with optimal chemotherapy and surgery, recurrence rates are high and survival is poor. Regular exercise can significantly improve physical and mental health during cancer treatment. We have shown that the immune response to the cancer can be improved by exercise also. Our study will help to determine the optimum level of exercise patients need to sustain before cancer surgery to produce this improved immune response. It is our expectation that our results will provide justification for introducing “personalised” exercise programmes to improve the immunotherapeutic treatment outcomes for oesophageal cancer, as well as empowering patients to help themselves fight their cancer” – Prof Adam Frampton

Grant title: Optimising prehabilitation exercise to enhance tumour outcomes in advanced oesophageal cancer

Background

Regular exercise can significantly improve physical and mental health during cancer treatment and reduce the time needed in the hospital. Animal studies suggest that exercise training can also reduce the number of cancer cells. For example, exercise training in mice produces more immune cells in the tumour. These immune cells in the tumour contribute to the destruction and reduction of the size of the tumour and are a vital component of effective immunotherapy (cancer treatment that helps your immune system fight cancer).

In humans, exercise training and the immune response in tumours are less understood. Only 1 study has investigated the effect of a single exercise session before surgical removal of the prostate in prostate cancer patients. As the benefits of exercise are gained from weeks/months of exercise, no effect on the immune cells in the tumours were found.

Following our published pre-surgery exercise versus control group assessing fitness changes in patients with oesophageal cancer, we took advantage of access to patient tumour tissues. We used thin slices of their tumour tissue and state-of-the-art methods to detect and visualise immune cells within the tumour. Compared with the controls, the exercise group had significantly more immune cells in their tumours, largely consisting of a critical subpopulation important for killing cancerous cells called CD8+ T cells. CD8+ T cells in tumours are associated with improved survival outcomes.

Critically, we detected positive associations between changes in patient aerobic fitness and the amount of these cells in the tumour. This suggests that if we increase fitness, we can increase the frequency of these cells in the tumour. Therefore, we propose performing a randomised clinical trial to determine the optimum level of exercise patients need to sustain before surgery to produce this improved immune response.

Aims and objectives

The trial will aim to understand how this happens and how the entry of immune cells into the tumour changes the environment around a tumour. We are a multidisciplinary team of exercise immunologists, tumour immunologists and clinicians working with the Human Performance Institute at the University of Surrey in collaboration with the Royal Surrey NHS Trust. We are capable of performing this clinical trial and translational research.

How it will be done

We will assess immune cell response in blood samples obtained from oesophageal cancer patients before, during and after a moderate-vigorous-intensity or low-intensity 16-week exercise programme. Following the exercise programme, tumour tissue removed at surgery from these patients will be used to investigate the presence and abundance of immune cells. We will use state-of-the-art technologies to identify different immune cell types, their functionality and their distribution within the tumour tissue.

Potential impact

A better understanding of this is crucial, as current anti-cancer immune-based therapeutics work best when there is a pre-existing immune response within the patient’s tumour. Generating evidence that exercise can improve the immune response against the tumour in patients with oesophageal cancer would provide significant justification for introducing “personalised” exercise programmes to improve immunotherapeutic treatment outcomes.