Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Almost 90% of deaths due to cancer occur when a tumor spreads (metastasizes) to other tissues in the body. Many solid cancers first spread to regional lymph nodes, and detection of these lesions predicts worse patient outcome. In the past, researchers believed that tumor cells were passively transported through the lymphatic circulation to nearby lymph nodes; however, recent evidence suggests that metastasis to these sites is an active process. For example, the lymph node closest to the tumor undergoes several changes prior to tumor cell arrival, including a shift in the balance between different types of immune cells that creates a more tolerant environment for incoming cancer cells. We have discovered that lymph nodes directly draining the tumor also have regions of low oxygen availability, a condition called hypoxia. A hypoxic environment is known to promote tumor aggression and suppress immune responses that would normally kill cancer cells; therefore, it is important to understand how lymph node hypoxia relates to cancer metastasis, and what effect it has on nearby immune cells. We will first determine whether low oxygen develops in the lymph nodes prior to tumor cell arrival, by labeling tumor cells with a fluorescent marker in order to track their movement. Since lymph nodes play an important role during the development of an effective immune response, we will also determine whether oxygen shortage inhibits the function of certain immune cell populations in the lymph node. The results will have important implications for the development of new therapies to help the immune system eradicate metastatic tumor cells in the lymph node.