Project 467091

Despite recent efforts to improve cancer diagnosis and treatment, the Canadian Cancer Society estimates that cancer will kill 1 in 4 Canadians. A reason for the high proportion of cancer-related deaths is the fact that tumours with low oxygen supply (hypoxia) are more likely to spread throughout the body (metastasize), as well as being resistant to current treatment options, like immunotherapy.Immunotherapy is a relatively new cancer treatment that attempts to improve immune cell responses to a tumour. An important immune cell responsible for killing tumours in response to immmunotherapy is the cytotoxic T cell. Since hypoxic tumours are resistant to immunotherapy, we hypothesize that the low oxygen within hypoxic tumours kills cytotoxic T cells and/or makes them non-functional.To test our hypothesis, we will grow mouse cytotoxic T cells in a petri dish at a very high oxygen level (21%), normal body oxygen level (5%), or in hypoxia (1%). This will allow us to compare the growth of the cells in all these conditions, as well as their tumour killing ability using additional laboratory techniques. As an example, we could compare the amount of toxic proteins the cytotoxic T cells make in response to stimulation when exposed to these different oxygen levels. Next, we will microscopically image cytotoxic T cells in mouse tumours to see if the cells are even capable of entering and living in hypoxic regions of tumours. In addition, the T cells in the tumours will be isolated and additional experiments will be done to test their tumour killing ability. By improving our understanding of how cytotoxic T cells behave in hypoxia, the research community can develop therapeutic strategies to improve immunotherapy in patients with hypoxic tumours.