Studies of T cell mediated tolerance indicate that a subpopulation of T cells, named regulatory T cells (Tregs) serve as a major negative influence on the immune system. These cells, characterised by expression of CD4 and the transcription factor, Foxp3, keep both innate and adaptive immune responses in check and suppress responses to both self- and non-self antigens. A clear objective of Treg research is to determine how they can be manipulated therapeutically to treat a wide range of immune-ba sed diseases. In my laboratory we have found, using mouse models and studies of patients with cancer, that tumours represent a defined location of Treg enrichment. This finding highlights the utility of studying tumours for the purpose of identifying conditions and mechanisms that facilitate Treg involvement in disease. The key goal of this project is to use tumours to identify mechanisms that promote or inhibit the involvement of Tregs in a given immune response. This informat ion will subsequently be utilised in the design of strategies to block or enhance the activity of the cells for immunotherapeutic purposes.