Grant: Project Grant

CD8+ T cells are part of the immune system and play a key role in eliminating cancerous cells in our body. CD8+ T cells are activated when they encounter tumour-expressed target proteins through their unique receptor, where each cell expresses a receptor that is unique for an individual target protein. This activation leads to differentiation and production of effector molecules, which is strongly linked to the activity of metabolic pathways that break down nutrients to produce both energy and cellular building blocks. The ability of CD8+ T cells to produce crucial effector molecules that are used to rid the body of cancerous cells is dependent on the metabolic breakdown of sugars (glucose), also referred to as glycolysis. In previously published work we showed that limiting the breakdown of glucose temporarily drives adaptations in CD8+ T cells that ultimately improved anti-cancer function of these cells. Although we could readily show differences in energy generating metabolic pathway activities, we do not know how CD8+ T cell function is regulated by these adaptations. In this proposal we aim to uncover the mechanisms that impact CD8 T cell activity against cancer, by investigating the pathways that sense glucose availability, metabolic pathway activity, and T cell activation through their target-specific receptor. This work will illuminate new targets that could be used to bolster CD8 T cell activity against cancer, and could provide insight into the lab-based generation of superior CD8 T cells for the treatment of and cancer.