Kynurenine metabolic pathway: implications for oncolytic virus-based cancer immunotherapy

Every year, worldwide, an estimated 9.6 million people die from cancer, clearly indicating an urgent need for new treatment options. Oncolytic virus (OV)-based cancer immunotherapy is considered as a promising modern-day innovation that can be used to cure cancers. Unfortunately, the full potential of OV-based therapies still remains unattained. Hence, this project is focused on synthesizing the knowledge that is essential to make OV therapies highly efficacious in clinics. Our latest discoveries have identified that the reprogramming of cell metabolism improves the efficacy of OV-based cancer therapies. Our on-going research has identified a new role for the kynurenine pathway (KP) of metabolism in clinically desired antitumor immunity against lung cancer. Hence, the overarching goal of the proposed research is to study the role of the KP metabolism in defining the efficacy of antitumor T cell immunity induced by OV-based therapy of lung cancer. To achieve our goal, we have developed a first-of-its-kind infrastructure and methodologies.Using these in-house advances, we will:1. Understand the effect of oncolytic reovirus on the KP metabolism in cancer and immune cells2. Evaluate how the KP metabolism governs immunological and metabolic fitness of OV-induced antitumor immunity3. Dissect the mechanisms by which the KP metabolism regulates OV-induced antitumor immunity against lung cancer Cancer immunotherapies, educating the immune system to fight cancer, have tremendous potential. However, these approaches show efficacy in only a limited number of patients. The immuno-metabolomics-based approach being investigated here, represents an outside-the-box solution to this problem. Although this project specifically focuses on lung cancer, many of the paradigms investigated also apply broadly to other cancer types. We truly believe that our findings will positively change the way we treat cancers, and aid our cumulative fight to reduce the cancer-related mortality in Canadians.