Enhancing the therapeutic potential of reovirus oncotherapy through the characterization and manipulation of myeloid-derived suppressor cells

Cancer is difficult to eradicate in part because of its ability to hide from the body's immune system. However, the treatments that elicit a strong immune attack against the tumor (through anti-tumor immunity) can eliminate cancer and prevent future relapse. Such anti-tumor immunity-inducing modalities, known as cancer immunotherapies, represent one of the best modern-day cancer treatment options. Nonetheless, inducing anti-tumor immunity is a daunting task as tumors use numerous suppressive strategies to evade detection and attack from the immune system. These mechanisms actively resist the initiation of anti-tumor immunity and thus represent an obstacle that needs to be understood and managed to enhance the effectiveness of immune-based therapies. Although viruses tend to be perceived as harmful agents, Dr. Patrick Lee found that reovirus, a benign human virus, selectively kills cancer cells while leaving normal cells unharmed. Owing to these anti-cancer benefits, reovirus is currently in phase III clinical trials. In addition, Dr. Lee has discovered that reovirus overturns the suppressive tumor environment and induces anti-tumor immunity. Thus, if properly managed, reovirus can be used for its direct cancer-killing actions and to manage tumor-associated suppression. It is now clear that these immunological benefits are the vital part of reovirus-based cancer therapy. Immune cells that are reprogrammed to become suppressive are now recognized as key mediators of tumor-associated suppression. These cells resist the development of anti-tumor immunity and promote tumor growth. Hence, the objectives of my project focus on: 1) understanding the interaction of reovirus with the suppressive immune cell mediators of tumor-associated suppression, and 2) applying this knowledge to design therapeutic entities to promote clinically meaningful anti-tumor immunity. This study bears tremendous clinical relevance and aims to enhance the efficacy of anti-cancer therapies.