Grant: Project Grant

Over the past several years, a new treatment option called immunotherapy, which stimulates the patient's own immune system to kill cancer cells, has been approved to treat several different cancer types. Tumours generally survive by evading attack from the immune system, and immunotherapy works best in patients with tumours that are more easily detected by the immune system. While immunotherapy can produce outstanding responses in 10-20% of patients with some tumour types, many tumours are harder for the immune system to recognize as harmful, and immunotherapy works in only a small fraction of patients with these cancers. A critical unmet need in immunotherapy research is a reliable way to predict which patients will benefit from this promising treatment option. Lymph nodes are small, bean-shaped organs located throughout the body, where immune responses to bacteria, viruses, and cancers develop. We have discovered that when a tumour is recognized by the immune system, nearby lymph nodes display regions of low oxygen (hypoxia) and we predict that cancer patients with hypoxic regions in their lymph nodes will benefit the most from immunotherapy. In this proposal, we will test whether the oxygen levels in lymph nodes can predict responses to immunotherapies currently used in the clinic. We will also determine how this low oxygen environment affects the ability of the immune system to kill cancer cells, and we will analyze the oxygenation status of lymph node samples from patients with breast cancer. This proposal will lay the foundation for future clinical studies to help oncologists direct immunotherapies to patients that are most likely to benefit from this remarkably effective therapy.