NKT cells and tumour immunosurveillance

虽然免疫系统有能力排斥肿瘤，但有时不会发生，导致癌症。有许多不同类型的细胞组成免疫系统，包括一些非常早反应的细胞，称为自然杀伤细胞（NK）和NKT细胞。这些细胞是对抗某些肿瘤的第一道防线，尽管我们不知道它们如何识别和响应肿瘤细胞。该项目的目的是研究NK和NKT细胞在应对一系列不同肿瘤类型中的功能重要性，包括黑色素瘤（皮肤癌），肺癌，乳腺癌和肉瘤（结缔组织肿瘤）。我们将通过将这些肿瘤注射到具有NK和/或NKT细胞特异性缺陷的小鼠中来测试这些亚群中的每一个的重要性。如果NK或NKT细胞很重要，那么当这些免疫细胞缺失时，肿瘤应该更有效地生长。我们还将能够将NK和/或NKT细胞放回小鼠体内，直接显示它们是肿瘤排斥反应的原因。使用这种细胞转移方法的修改，我们将能够抑制这些细胞通常产生的特殊分子，这些分子帮助它们与其他细胞相互作用，并帮助它们攻击肿瘤细胞。总的来说，本申请中概述的方法使我们能够确定哪些类型的细胞在应对广泛的不同肿瘤类型时是重要的，并且还应该告诉我们这些细胞如何能够攻击肿瘤。这些信息对于开发利用患者免疫系统攻击癌症的新策略（称为免疫疗法）将是非常宝贵的。

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).