Investigating anti-tumour T cell responses in nasopharyngeal carcinoma to refine vaccine-based immunotherapies

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Nasopharyngeal carcinoma (NPC) is a type of cancer that occurs at the back of the nose. It is unusually common in some parts of the world, including countries like Malaysia where it constitutes a very significant health problem. NPC can be cured, but in many cases the cancer comes back and this is usually fatal. Furthermore, patients who do survive are often left with significant long-term side effects caused by the toxic treatments. Therefore, new treatments are needed to reduce deaths from NPC and improve the quality of life for survivors. All patients with NPC have a virus, known as the Epstein-Barr virus, or EBV for short, in their tumour cells. We have developed a vaccine that can recognise EBV with the aim of boosting the patients' own immune response to the tumour. Early tests of our vaccine in people show that it is safe and that it can boost immunity against the virus. In this proposal we want to understand more about immunity to EBV in patients with NPC so that we can modify how we deliver our vaccine and eventually combine it with other drugs to improve its therapeutic effects. To do this we will be using new sequencing technologies to probe how patient's T cells, the body's main weapon against virus-infected cells, respond to EBV, for example before and after treatment, enabling us to 'track' individual T cell responses over time. At the same time, we will explore the nature of potential inhibitory pathways present in the tumour so that we might eventually target these in combination with our vaccine making it more effective.