T Cells

To learn about the effects of naproxen and aspirin on the normal colon in people with Lynch Syndrome.

296 million people worldwide are infected with the hepatitis B virus (HBV), despite the existence of an effective prophylactic vaccine. Current treatments (nucleoside analogues and pegylated interferon-α) do not prevent chronic hepatitis B (CHB) patients from developing liver fibrosis or hepatocellular carcinoma. Vaccination is the best way to prevent HBV infection. The first generation of plasma-based vaccines, introduced in the 1980s, has now been superseded by protein vaccines, which are the only ones authorized in France. They are safe and effective. After an initial series of three out of four doses, protective levels of antibodies to the HBV surface antigen (anti-HBsAg; ≥10 IU/mL) are achieved in over 95% of infants, children and young adults. HBV antigen (Ag)-specific CD4+ and CD8+ T lymphocytes play a major role in the control of HBV infection, contributing to viral clearance and the pathophysiology of acute hepatitis B. However, during HBC, these HBV-specific T cells develop a dysfunctional phenotype and become 'exhausted'. T lymphocytes directed against surface protein antigens (HBsAg) are the most affected by depletion mechanisms - these disappear completely in chronically infected patients, suggesting an important role for these T lymphocytes in infection control. Interestingly, recent studies of rare patients undergoing functional recovery from chronic infection following antiviral treatment have shown a re-emergence of T lymphocytes directed against HBsAg, confirming the importance of these cells in controlling viral replication. Although the protection induced by hepatitis B vaccination has mainly been attributed to the humoral response, a few studies have documented the presence of HBsAg-specific T lymphocytes. These could contribute to the maintenance of a long-term post-vaccination humoral response. The aim of this study is therefore to determine the frequency of healthy individuals receiving HBV vaccination who have a detectable HBsAg-specific T-cell response post-vaccination. We will also study the potential correlation between the frequency of HBsAg-specific T lymphocytes and the level of serum anti-HBsAg antibodies, and we will finely characterize the functional phenotype of these cells using cutting-edge methods and technologies (spectral cytometry, sequencing of mRNA and TCRs). These data will contribute to a better understanding of the biological mechanisms associated with HBV vaccine-induced protection.

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 the 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. The investigators have carried out a previous study looking at how exercise affects fitness before major surgery. After this they used state-of-the-art methods to detect and visualise immune cells within the tumour. Compared with the patients who did not exercise, the exercise group had significantly more immune cells in their tumours, consisting of a group of cells that are important for killing cancerous cells called CD8+ T cells. CD8+ T cells in tumours are associated with improved survival outcomes. Importantly, they found a link between changes in fitness and the amount of these cells in the tumour. This suggests that if there is increase in fitness, there also an increase in the frequency of these cells in the tumour. Therefore, the investigators propose performing a clinical trial to find out the best level of exercise patients need to sustain before surgery to produce this improved immune response. 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. The investigators consist of a 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. How it will be done The investigators will assess immune cell response in blood samples obtained from oesophageal cancer patients before, during and after a high or low intensity exercise programme. Following the exercise programme, tumour tissue removed at surgery from these patients will be used to investigate the the presence and quantity of these immune cells. Potential impact A better understanding of this is important, as current anti-cancer immune-based therapeutics work best when there is a an 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 treatment outcomes.