The identity, role and function of immune cells at sites of metastasis in cancer

The Tumour Microenvironment Laboratory focuses on how specific processes between cancer cells and surrounding non-tumour stromal cells influence cancer progression and metastasis to distant organs. A key goal is the translation of this understanding to novel clinical diagnostic and therapeutic approaches.
In particular, our work aims to understand how low oxygen (hypoxic) environments and other stress conditions change the physiology between tumour cells and stromal cell lineages. Additionally, we aim to understand the role hypoxia plays in generating receptive secondary metastatic sites (pre-metastatic niches). The work conducted in the Tumour Microenvironment Laboratory is focused on the translation of research findings to benefit patients.

Immune cells are key mediators of anti-tumour and pro-tumour functions, at both the primary and metastatic sites of solid cancers. While the role of monocyte-derived cells at the primary site of cancer is slowly being understood, our understanding about the role and composition of immune cells at metastatic sites is much less developed. We have generated unique syngeneic cancer models, utilizing fluorescently marked immune and tumours cells, to assess the immune cell infiltrate at metastatic sites. We found that immune cell infiltration into metastatic sites is directed and orchestrated by the primary tumours, and results in a permissive environment for metastatic outgrowth. Cancer cells coordinate these premetastatic environments through the secretion of cytokines and small vesicles, including exosomes.

In this project, bone marrow chimeras and orthotopic cancer mouse models will be used to determine the composition and function of the immune cell infiltrate at metastatic sites. Using flow cytometry and immunohistology, the immune cell lineages will be investigated in great detail. Which specific immune cells are required for establishing metastases will be determined by individual ablation of subclasses in bone marrow. Isolated immune cells will be assessed for function by measuring cytokine production. The driving factors for these immune cell alterations will be evaluated comprehensively by assessing cancer cell-derived factors, including cytokines and extracellular vesicles.
These experiments will provide an insight into the metastatic progression of cancer and will be the first of their kind. Ultimately, the goal is to understand the identity, role and function of immune cells at metastatic sites, and explore the potential to use this information to reduce metastatic tumour burden in 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, extracellular vesicle biology and other basic cellular immunology techniques.