Immune cells are key mediators of anti-tumour and pro-tumour functions at both the primary and metastatic sites of breast cancer. While the role of monocyte derived cells at the primary site of breast cancer is slowly being understood, there is very little known about the role and composition of immune cells at metastatic sites. We have generated a unique breast cancer model, utilising fluorescently marked immune and tumours cells, to assess the immune cell infiltrate at metastatic sites in breast cancer. We found that immune cell infiltration into metastatic sites is directed and orchestrated by the primary tumours, and results in a permissive environment at secondary sites for metastatic outgrowth.
In this project, bone marrow chimeras and orthotopic breast cancer mouse models will be used to determine the composition and function of the immune cell infiltrate at the metastatic site. Using FACS and immunohistology, the immune cell lineages will be investigated in great detail. Isolated immune cells, which are induced by tumours to populate the metastatic site, will be assessed for their cytokine production. Furthermore, the frequency of metastasis will be assessed in experiments where the immune cell lineages which populate the metastatic site have been ablated. These experiments will provide an insight into the metastatic progression of breast cancer and will be the first of their kind. Ultimately the goal is to understand the identity, role and function of immune cells at the metastatic site and explore the potential to use this information to reduce metastatic tumour burden in breast cancer patients. Students will have access to unique reagents and mice, and will acquire skills in mouse tumour model experimentation, immune cell isolation, multi-colour flow cytometry, IHC, and other basic cellular immunology techniques.
- Suitable for Honours, PhD or clinical students.