Grant: Travel Awards - Institute Community Support

There are many barriers to successful cancer treatment, including the ability of cancer cells to resist immune destruction and chemotherapy. Normally, immune cells can recognize cancer cells and destroy them. However, tumour cells can evade immune-mediated death by displaying molecules on their surface that inactivate these immune cells. One of these molecules is Programmed Death Ligand 1 (PD-L1); PD-L1 binds to a molecule known as Programmed Death 1 (PD-1) on immune cells. This interaction leads to inactivation of immune cells that would normally kill the tumour cells. For this reason, there are many new and exciting therapies aimed at blocking this interaction. Some of these treatments have shown encouraging clinical responses in certain types of cancer. While much is known about how these molecules affect the immune cells, little is known about whether this interaction has any effect on the cancer cell. We have evidence that the PD-1/PD-L1 interaction increases malignant properties of tumour cells, such as resistance to chemotherapy and increased growth rates. Thus, on top of having a role in inactivating immune cells, we hypothesize that the PD-1/PD-L1 interaction endows tumour cells with aggressive properties. We are currently using cell-culture and animal-based experiments to test this hypothesis. Our recent studies have shown that the binding of PD-1 on immune cells to PD-L1 on tumour cells increases signalling pathways that are important for tumour cell development and aggressiveness. We have also found that the PD-1/PD-L1 interaction increases invasiveness of tumour cells. We are continuing experiments to further elucidate how the PD-1/PD-L1 immune checkpoint increases the invasiveness of cancer cells. These studies are important because they could help us improve therapies designed to target the PD-1/PD-L1 immune checkpoint, to eventually improve patient outcomes.