NKT cells and tumour immunosurveillance

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Although the immune system has the ability to reject tumours, this sometimes does not occur, leading to cancer. There are many different types of cells that make up the immune system, including some which respond very early, called natural killer (NK) and NKT cells. These cells are the first line of defence against some tumours, although we do not understand how they recognise and respond to tumour cells. The aim of this project is to investigate the functional importance of both NK and NKT cells in response to a range of different tumour types, including melanoma (skin cancer), lung carcinoma, breast carcinoma and sarcoma (connective tissue tumour). We will test the importance of each of these subsets by injecting these tumours into mice that have specific deficiencies in NK and-or NKT cells. If the NK or NKT cells are important, the tumours should grow more effectively when these immune cells are absent. We will also be able to put NK and-or NKT cells back into the mice to show directly that they are responsible for tumour rejection. Using a modification of this cell transfer approach, we will be able to inhibit special molecules that are normally produced by these cells that help them interact with other cells, and also help them attack the tumour cells. Collectively, the approaches outlined in this application allow us to determine which types of cells are important in response to a broad range of different tumour types, and also should tell us how these cells are able to attack the tumours. This information will be invaluable for the development of new strategies to use the patients immune system to attack cancer (known as immuno-therapy).