Grant: Doctoral Research Award: Canada Graduate Scholarships

One of the most successful treatments for blood cancer such as lymphoma is CAR (chimeric antigen receptor) T cell therapy which consists of isolating and engineering a patient's own killer T cells (a type of white blood cell) to directly target a patient's own cancer cells. However, these CAR T cells have struggled to treat patients with solid tumours like breast cancer. One of the reasons is that these solid tumours can form hostile low oxygen regions called hypoxia. In our model, we have observed that T cells exposed to hypoxia produce more proteins that directly kill tumour cells. However, hypoxia also appears to impair T cell growth, survival, and production of molecules that improve global immune activity against tumour cells. Interestingly, we have found that we can reverse some of the impaired effects by supplementing hypoxic T cells with an important nutrient known as pyruvate. From these results, we think that exposing T cells to both hypoxia and pyruvate outside of the body will be a method that significantly improves solid tumour killing when these cells are reinjected back into a host with a solid tumour. To understand how pyruvate improves the function of T cells, we will be conducting experiments on how pyruvate alters pathways that are known to be important for T cells. After we determine mechanistically how pyruvate improves T cell function, we will inject hypoxia and pyruvate-exposed T cells into mice that have a solid tumour to see if our pre-exposure method can help shrink solid tumours in an animal model. Understanding how hypoxia and pyruvate improves T cells will provide new insight into T cell biology while also providing a method to better prepare T cells for CAR T cell therapy.