Rationale: Breast cancer (BCa) is the most frequently diagnosed cancer in Australia and its incidence has been steadily increasing over the recent decades. Immunotherapy is the newest pillar of cancer therapy and is showing great promise in advanced melanoma and lung cancer and within triple negative breast cancer. It has not yet been utilized in in-situ disease or as a cancer preventative. To extend immunotherapy to earlier stages of disease, we need to characterize the immune environment as the cancer develops.
Methods: We sought to develop tools to define the pro-tumour and anti-tumour immune microenvironment in the mouse mammary glands such that we could use it to assess the immune response in our transgenic mouse models of BCa. We have data indicating macrophages are particularly important in early BCa development and therefore also focussed on developing assays that also allow us to assess macrophage functional activity.
Results: We have developed 2 multi-parameter FACS panels to assess the innate and adaptive immune cells in the mouse mammary glands and early breast lesions. This includes numerous DC and macrophage subtypes, T cells and pro/anti-tumour T cell cytokines. Simultaneously, we shown that the pro-tumour macrophages can be identified through increased oxygen consumption rates in a metabolic flux analysis. They can also supress T cell function in co-culture experiments. Studies are now underway using these tools in our mouse models of early breast cancer. Phagocytosis assays were not able to clearly define the pro and anti-tumour macrophages.
Conclusion: We have developed tools to allow us to define the immune microenvironment of breast cancer initiation, such that we better understand the immune response and also impact of immune modulating therapies.