Diffuse large B cell lymphoma is the commonest lymphoma and is highly aggressive. A significant number of patients fail existing treatments and 30% of patients will die from their disease. These tumours frequently appear to have avoided immune responses directed against them, although how they avoid these responses and the identity of the immune targets in the cancer cells are poorly understood. Improving our understanding of these fundamental processes may lead to improved treatments for DLBCL that work by restoring or enhancing immune responses against the tumour.
The most aggressive form of DLBCL carries the Epstein-Barr virus (EBV) and the cancer cells of EBV-DLBCL contain viral proteins that, being totally foreign to the immune system, should be easy targets for the immune system to recognise. How these tumours develop, avoiding the strong anti-viral immunity present in most people, is unknown. The role of the virus in this disease is also unknown.
Our laboratory has extensive experience of characterising EBV and the immune response against it. Based on this work we have made a cancer vaccine for patients with EBV-positive cancer. The vaccine boosts immune responses against EBV proteins that are present in tumour cells and is currently being tested in EBV-associated head and neck cancer. We want to apply the vaccine to EBV-DLBCL as well, but doing so requires better understanding of how the tumour cells avoid immune responses. This knowledge will help us to use the vaccine in the correct way, maximising its ability to work in patients.
We will therefore collect blood and tumour samples from patients with EBV-DLBCL to identify the immune defects that allow the disease to develop. We will also study the role the virus plays in the disease. We will study patients with EBV-DLBCL and patients whose tumour doesn't carry the virus. Comparing data from both sets of patients will teach us more about DLBCL in general, help us to identify the best way to use the vaccine in EBV-DLBCL and aid the development of new immunotherapies for all DLBCL patients.