Dissecting the impact of L-selectin on T lymphocyte dependent tumour immunity

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The harnessing of one's own immune system to treat a cancer, termed tumour immunotherapy, is an extremely attractive proposition because of the potential for combining high selectivity with low toxicity. Tumour immunotherapy has progressed significantly in recent years with improved understanding of how to boost the normally weak immune response to tumours. Nevertheless, there is considerable need for more improvements to ensure this form of treatment is more widely and effectively applied. Successful immunotherapy depends on immune cells, such as killer T lymphocytes, becoming activated and homing to the tumour. However, tumour blood vessels limit access of T lymphocytes to the tumour. We have found that T lymphocytes are better equipped to control tumour growth when they express the homing molecule L-selectin. We predict this is because L-selectin expression factilitates access of killer T cells to the tumour where they can deliver their lethal hit. The aim of this proposal is to study the properties of these L-selectin enhanced T lymphocytes and to determine whether they could be used to treat tumours. The potential long-term benefit of this work is that it will direct novel strategies for improving the clinical application of tumour immunotherapy.