Understanding and targeting the distinct immunosuppressive functions of thymic and induced CD4+ regulatory T (Treg) cells

肿瘤在免疫活性宿主中的生长与免疫系统识别和杀死癌细胞的强大能力不一致。癌症免疫编辑假说已被提出作为解释这种行为的概念框架。根据这一假设，肿瘤发展的特征是初始的“消除”阶段，在此期间，大多数癌细胞被免疫系统的各种成分破坏。随后是“平衡”阶段，在此期间，来自免疫系统的压力有助于选择肿瘤变体，从而产生“逃逸”阶段，其特征在于逃避免疫控制和无限制的肿瘤生长。虽然抗原丢失变体的选择代表了肿瘤逃逸的机制，但它未能解释为什么已建立的肿瘤继续表达被肿瘤浸润淋巴细胞识别的免疫原性表位。通过理解免疫抑制在促进肿瘤逃逸中的关键作用，可以更好地解释含有免疫原性表位的肿瘤的生长。该项目旨在研究肿瘤内免疫功能被抑制的机制。特别是，我们专注于表征微环境因素和T细胞免疫抑制的内在机制，以及肿瘤细胞对宿主免疫的适应。

Growth of tumours In immunocompetent hosts is at odds with the powerful ability of the immune system to recognize and kill cancer cells. The cancer immunoeditlng hypothesis has been proposed as a conceptual framework to account for this behaviour. According to this hypothesis, tumour development is characterized by an initial 'elimination' phase, during which a majority of cancer cells are destroyed by various components of the immune system. This is followed by an 'equilibrium' phase, during which pressure from the immune system contributes to selection of tumour variants that give rise to an 'escape' phase characterized by evasion from immune control and unrestrained tumour growth. While selection of antigen-loss variants represents a mechanism of tumour escape, it fails to explain why established tumours continue to express immunogenic epitopes that are recognized by tumour infiltrating lymphocytes. Growth of tumours containing immunogenic epitopes is better explained through an understanding of the critical role of immunosuppression in promoting tumour escape. This project aims to investigate the mechanisms by which immune function Is suppressed within tumours. In particular, we are focussed on characterising microenvironmental factors and T cell-intrinsic mechanisms of lmmunosuppression, and adaptations by tumour cells to host immunity.