Intravital imaging as a platform for screening checkpoint and focal adhesion kinase inhibitors as potential treatment for cancer metastasis

Despite new developments in treatment, cancer remains the second leading cause of death worldwide. Breast cancer is the most common cancer within the UK, with death generally caused by the formation of metastasis.

I intend to investigate the hypothesis that immune responses at the metastatic site determine the long-term outcome of therapy.

I will compare immune responses at the primary and metastatic sites upon administration of checkpoint inhibitors that have different clinical success rates. Flow cytometry and t-SNE analysis will provide insight into the affected cell populations and timings.

I will then utilise newly developed intravital imaging technologies to visualise immune responses in vivo at multiple cancer sites. I will measure cytotoxic cell activity and tumour cell death as indicators for anti-cancer response.

Further, I will examine the ability of a combination of checkpoint inhibitor and focal adhesion kinase inhibitor to fully eradicate tumour cells.

An inhibitor will be fluorescently tagged to study its access to tissue and interaction with immune cells dependent on combination therapy.

The proposed research will help to elucidate the role of immunotherapy on the metastatic foci and will provide the first insights into the benefit and limitations of combination therapy on secondary site immune responses.