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

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.