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

鼻咽癌（NPC）是一种发生在鼻子后部的癌症。它在世界上的一些地方非常普遍，包括像马来西亚这样的国家，它构成了一个非常严重的健康问题。鼻咽癌是可以治愈的，但在很多情况下，癌症会复发，这通常是致命的。此外，幸存下来的患者往往会因有毒治疗而留下严重的长期副作用。因此，需要新的治疗方法来减少鼻咽癌的死亡，提高幸存者的生活质量。所有鼻咽癌患者的肿瘤细胞中都有一种被称为eb病毒（EBV）的病毒。我们已经开发出一种能够识别EBV的疫苗，目的是增强患者自身对肿瘤的免疫反应。我们的疫苗在人体上的早期测试表明，它是安全的，可以增强对病毒的免疫力。在这个提议中，我们希望更多地了解鼻咽癌患者对EBV的免疫，以便我们可以修改我们的疫苗的递送方式，并最终将其与其他药物联合使用，以提高其治疗效果。为了做到这一点，我们将使用新的测序技术来探测患者的T细胞（身体对抗病毒感染细胞的主要武器）如何对EBV做出反应，例如在治疗前后，使我们能够“跟踪”个体T细胞随时间的反应。同时，我们将探索肿瘤中存在的潜在抑制途径的性质，以便我们最终可以将这些途径与我们的疫苗结合起来，使其更有效。

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.