Grant: Banting Postdoctoral Fellowship Program

Most of the time, the immune cells in your body do a great job of killing cancer cells. Unfortunately, a tumour has the ability to suppress the immune system, sometimes turning anti-tumour immune cells into pro-tumour immune cells. In fact, over 50% of a tumour's mass can be made up of immune cells alone! This is why some of the best cancer therapies to date work by turning the immune system back on. Unfortunately, for breast cancer patients, and especially those with the particularly aggressive "triple-negative" form of breast cancer, current immune targeting therapies are not very effective. Interestingly, breast cancer prognosis is related to the density of neurons in tissues, and there is evidence that by removing neurons, cancer growth is reduced. In non-cancer settings, such as infection, it has been shown that neurons can control the immune system. In this project, we propose to test the hypothesis that neurons in breast cancer tumours can suppress the immune system. This will lead to the development of novel therapies that activate the immune system by targeting neurons. To study this, we will model breast cancer growth in mice and then block the sensory neurons from firing. Then, we will look at changes in immune cells from the tumour using an advanced technique called time-of-flight mass cytometry, which allows us to measure over 20 different cell types at once. Next, intravital microscopy will be carried out on tumour sites, before and after blocking neurons, to look at immune cell behaviour. Finally, we will design an in vitro culture system where neurons and cancer mini-organs will be grown together in a dish. This will allow us to use single cell RNA sequencing to see if the tumours are secreting something that changes the expression of genes by neurons. All of this data together will provide new information on therapeutic avenues for breast cancer.