Despite new developments in treatment, cancer remains the second leading cause of death worldwide. Breast cancer is the most common cancer within the UK, with death generally caused by the formation of metastasis. I intend to investigate the hypothesis that immune responses at the metastatic site determine the long-term outcome of therapy. I will compare immune responses at the primary and metastatic sites upon administration of checkpoint inhibitors that have different clinical success rates. Flow cytometry and t-SNE analysis will provide insight into the affected cell populations and timings. I will then utilise newly developed intravital imaging technologies to visualise immune responses in vivo at multiple cancer sites. I will measure cytotoxic cell activity and tumour cell death as indicators for anti-cancer response. Further, I will examine the ability of a combination of checkpoint inhibitor and focal adhesion kinase inhibitor to fully eradicate tumour cells. An inhibitor will be fluorescently tagged to study its access to tissue and interaction with immune cells dependent on combination therapy. The proposed research will help to elucidate the role of immunotherapy on the metastatic foci and will provide the first insights into the benefit and limitations of combination therapy on secondary site immune responses. One in six lives are cut short by cancer, with approximately 90% of mortality caused by spreading of the tumour, also called metastasis. I propose to investigate whether cells from our immune system found in secondary tumours contribute to the efficacy of drugs used in breast cancer patients. I will utilise newly developed techniques to visualise how immune cells function in living animal models of breast cancer, and will compare the efficacy of drugs in primary and secondary tumours. I will measure the anti-tumour activity of immune cells as well as how well they bind to tumour cells. Further, I will investigate how therapies that use more than one drug simultaneously act to eradicate metastatic tumours, studying how clinical treatments enter the metastatic site and fulfil their role. My studies will provide insight into the limitations of current therapies to support the design of new, more effective therapies.