Grant: CIHR Fellowship

Our immune system is responsible for the protection of our body, by detecting and destroying cells that are cancerous. However, sometime our immune system fails to detect a problem, leading to the development of cancer. In pediatric cancer, we know that CD8 T cells fail to destroy cancerous cells. But what are CD8 T cells? CD8 T cells are white blood cells specialized in the detection and the attack of cancer cells. They travel throughout our bodies and find cancer cells. Like us, CD8 T cells need to "eat" to stay alive, to move, and to function normally. Without nutrients, CD8 T cells don't have the ability to fight off cancerous cells. These nutrients are needed to generate energy, and building blocks (called metabolites) for growth both to exert their protective functions. What is the link between nutrients, CD8 T cells, and cancer? In the context of cancer, there is a fight for nutrients between CD8 T cells and cancerous cells. CD8 T cells have to quickly adapt when they are in this competition, to make sure they maintain their protective functions. We know that CD8 T cells have the ability to rapidly switch from using nutrients to make building blocks to burning nutrients to make energy, but we do not understand how this is regulated. The aim of my project is to understand how CD8 T cells know which nutrients are around them, and how they "choose" to switch between building and burning. By growing CD8 T cells in a laboratory setting, we can change nutrient availability and measure the changes in T cell anti-cancer functions. Why is it important? From a previous study, we know that CD8 T cells grown in a laboratory setting, after restricting their food, followed by re-feed, they provide better protection against cancer. Understanding how CD8 T cells "eat" and use their nutrients to make building blocks to grow or generate energy to kill cancer cells will help develop better therapies or increase the efficacy of current therapies to treat pediatric cancer.