Emerging evidence indicates that immune cells are mobilized and activated in the tumour microenvironment (TME) during metastatic cancer progression. The TME is also altered following various anticancer therapies, which can paradoxically contribute to a lack of response/acquired resistance to treatment. In particular, inflammation can promote metastatic progression. We will systematically focus on different immune cell types whose levels vary across systemic inflammation, in specific tissues – including the brain, and whose variations are further exacerbated by the presence of a primary tumour. We will determine whether this translates to increased cancer metastasis to this site, and the potential dependency on specific cytokines or factors. Subsequent genetic, chemical or biological studies will follow to confirm the causality of these mechanisms to the metastatic phenotype. The underlying mechanistic contribution of the microenvironment to metastasis and therapeutic resistance will be based on a range of complementary techniques including mouse models of cancer, 3D co-culture systems, computational approaches, and analysis of patient samples in collaboration with our clinical colleagues.