Grant: Master's Award: Canada Graduate Scholarships

Immune checkpoints are vital regulators of the host immune system. They provide a balance between co-stimulators and inhibitors of immune cells, preventing over-stimulation that can otherwise lead to inflammation and auto-immunity. However, tumour cells can take advantage of this innate system as a way to deactivate immune cells and evade the host immune system, termed immune escape. Programmed Death 1 (PD-1) is one such immune checkpoint found on immune cells. It interacts with Programmed Death-Ligand 1 (PD-L1) on tumour cells and results in the deactivation of immune cells, conferring immune escape. Strategies have been developed to interfere with this PD-1/PD-L1 interaction, including drugs called immune checkpoint blockers. These immune checkpoint blockers have demonstrated exceptionally high response rates in patients with advanced stages of cancer, providing new promise. However, there are limitations to the current use of immune checkpoint blockers. For reasons not yet known, the majority of patients do not significantly benefit from this therapy, despite the high response rates. This demonstrates that there is still a lot to be known about the PD-1/PD-L1 axis. Quite recent research has elucidated that the PD-1/PD-L1 interaction not only affects immune cells, but also exerts a change on the tumour cells, causing them to exhibit a more malignant phenotype, including drug resistance and metastasis. Our proposed research aims to identify proteins within the tumour cells interacting with PD-L1 that facilitate malignant progression. This knowledge would provide us greater insight into the underpinnings of immune checkpoints, and could ultimately impact the timing of therapies as well as potentially elucidate new druggable targets.