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

利用自己的免疫系统来治疗癌症，被称为肿瘤免疫疗法，是一个非常有吸引力的命题，因为它有可能结合高选择性和低毒性。近年来，随着人们对如何提高对肿瘤通常较弱的免疫反应的理解，肿瘤免疫治疗取得了显着进展。然而，仍有相当多的改进需要，以确保这种形式的治疗得到更广泛和有效的应用。成功的免疫治疗依赖于免疫细胞，如杀伤T淋巴细胞，被激活并归巢于肿瘤。然而，肿瘤血管限制了T淋巴细胞对肿瘤的访问。我们发现，当T淋巴细胞表达归巢分子L-选择素时，它们更有能力控制肿瘤的生长。我们预测这是因为L-选择素的表达使杀伤T细胞接触肿瘤的途径变得容易，在那里它们可以提供致命的打击。该方案的目的是研究这些L-选择素增强的T淋巴细胞的特性，并确定它们是否可以用于治疗肿瘤。这项工作的潜在长期好处是，它将指导改进肿瘤免疫治疗临床应用的新策略。

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.