The molecular mechanisms of breast cancer spread to distant sites and the influence of immune surveillance in preventing metastatic outgrowth are largely unknown. We recently combined the use of our unique syngeneic 4T1.2 model of spontaneous metastasis to bone with expression profiling of immunopurified tumour cells, to analyse tumour cell-specific alterations that occur when tumours spread from the primary site to the bone in an immunocompetent system. This study revealed that primary breast tumour cells express an innate immune pathway that is regulated by interferon regulatory factor 7 (Irf7), and that upon spread to the bone there is a dramatic decrease in the expression of this pathway. Restoration of tumour cell Irf7 signalling suppresses metastasis to bone in an immune dependent manner suggesting that tumour cells directly stimulate anti-tumour immune responses via secretion of type I IFNs. Additionally, loss of the type I IFN receptor in the host stroma (Ifnar1-/- Balb/c mice) accelerated metastasis to bone in orthotropic and spontaneous mammary tumour models, suggesting that cross-talk between tumour cells and the immune system (by secretion of type I IFN) dictates bone metastasis in breast cancer. Our work is now focused on identifying the immune responses that are stimulated by tumour cell interferon secretion and are critical for metastasis suppression.