Grant: Master's Award: Canada Graduate Scholarships

Radiotherapy is a standard therapy used to reduce tumors before surgery or prevent tumor recurrence after surgery. Although radiotherapy has been developed to directly kill cancer cells, it occasionally induces systemic anticancer responses known as the abscopal effect. The immune system normally recognizes and kills cancerous cells, however, tumors develop when they acquire the ability to escape from the immune system by suppressing the anticancer immunity. Thus, if the suppressed immune system could be reactivated during radiotherapy, the tumor recurrence would be reduced. Cell irradiation kills cancer cells by activating intracellular pathways for programmed cell deaths (PCD) such as apoptosis, necroptosis and pyroptosis. Apoptosis is a non-immunogenic cell death that does not cause immune activation. In contrast, necroptosis and pyroptosis are inflammatory cell deaths that release inflammatory mediators with tumor antigens during the process. In this study, we hypothesise that the induction of inflammatory cell death is the key step to activating anticancer immunity during radiotherapy. The objective is to find potential approaches to promote cell irradiation-induced inflammatory cell death by modulating the intracellular PCD pathways. To this end, I will determine whether inflammatory cell death can be induced during radiotherapy in different breast cancer cell lines. I will conduct western blot analysis for PCD markers and cytokine ELISA. I will determine if treatment with a caspase-8 inhibitor or IFN-? will promote inflammatory cell death during cell irradiation. Caspase-8 initiates the induction of apoptosis but simultaneously inhibits necroptosis. IFN-? is an immune regulatory cytokine that stimulates the pyroptosis pathway and induces anti-apoptotic proteins.