A novel function for interferon-gamma in preventing T-cell lymphoma

Interferon-gamma (IFNg) is pleiotropic cytokine that is important for anti-tumour immunity by activating cytotoxic lymphocytes and macrophages, and by acting directly on tumour cells to suppress their proliferation and induce apoptosis. Consistent with this, IFNg deficient mice exhibit a high incidence of T-cell lymphomas. However, IFNg may in fact be important in the process of lymphomagenesis (i.e. development of the malignancy), as opposed to immune responses to the lymphoma. Our hypothesis is that IFNg regulates MHC-antigen presentation in the thymus and that this is required for the establishment of the T cell lineage transcriptome program within developing thymocytes. We propose that a loss of IFNg signalling disrupts this process, resulting in lineage plasticity and transformation of developing thymocytes into lymphoma cells. This project will investigate this hypothesis by analysing a mouse model with genetic deficiency for IFNg signalling.