Dissecting the roles of tissue-resident macrophages in tumorigenesis

Macrophages are best known for their immune functions, but they also play important roles in development and tissue homeostasis – often referred to as trophic functions. There are two distinct lineages of macrophages that populate mammalian tissues; embryo-derived tissue-resident macrophages (TRM) maintain themselves in adult tissues by proliferation and self-renewal and coexist with monocyte-derived macrophages (MDM) from adult bone marrow. We recently showed that TRM form a niche that promotes the metastatic spread of cancer cells, suggesting TRM have specific functions linked to tumour progression. We hypothesise that TRM maintain hard-wired trophic functions that support the malignant progression of cancer cells and tumorigenesis. It’s therefore critical to determine the unique features of TRM and the mechanisms that maintain their homeostasis and functional programming during tumour development. In this project we will perform high-dimensional single cell analysis of TRM in mouse models and human cancer. We will develop new genetic tools to dissect the specific functions of TRM during tumorigenesis and the mechanisms that maintain their homeostasis and functional programming. These studies will give new insights into the biology of TRM and their roles cancer that may reveal new targets for therapeutic intervention.