Belinda Parker

From the loss of myoepithelial cell barriers in the transition from ductal carcinoma in situ to invasive carcinoma in breast cancer to the induction of tumour cell loss of immunogenicity markers during breast and prostate metastasis, our laboratory utilises both mouse and human systems in conjunction with cutting-edge techniques (robotic 3D systems, multiplex immunohistochemistry) to explore how interactions and cellular alterations in the TME shape cancer progression. We are currently evaluating how novel biomarkers that we have discovered through high-throughput RNA and protein screens in several stages of solid cancers can be exploited as identifiers and targets of tumour growth, invasion and spread.

We use various immune-activating compounds (HDAC inhibitors, viral mimetics, cytokine inducers) in different systems (in vitro, ex vivo & in vivo inc. PDX/explants) to investigate how we can promote long-term immune responses against tumour cells. Preclinical and retrospective patient studies enable us to assess the synergy of immune-targeted agents with conventional treatment, such as chemotherapy and hormone deprivation. We can also determine how patients may respond to therapy and stratify subsets of patients that may benefit from personalised treatment regimens through rigorous immune profiling.

Several of our investigations have revealed the importance of tumour-intrinsic immune signaling pathways, particularly those drive by the type I interferon (IFN) family cytokines, in bone metastasis—a common site of tumour cell spread in both prostate and breast cancer that is currently incurable. Loss of this pathway in cancer cells can accelerate bone metastases and promotes changes in the osteoimmune TME to permit tumour expansion. Our continued research into how this loss can be both induced and reversed is critical to the promotion of tumour cell visibility in bone to immune effector cells and sustained tumour clearance.