Mechanisms of natural killer T (NKT) cell development, homing, and activation

The body?s natural defense systems are usually very good at detecting and eliminating abnormal or damaged cells. However, abnormal cells can sometimes gain advantages that allow them to avoid or overwhelm these defenses and establish harmful tumours. Dr Johnston?s laboratory has been working to examine how a population of white blood cells called natural killer T (NKT) cells can be activated to enhance the recognition and elimination of cancer cells.NKT cells appear to play natural roles in preventing the formation of tumours as mice lacking these cells are more likley to develop cancer. Similarly, NKT cells are often reduced in cancer patients and NKT cell infiltration into tumours has been associated with increased chances of survival. In mice, NKT cells can be activated to provide effective protection against the spread of many types of cancer cells. However, there is relatively little known about how NKT cells work. Dr Johnston?s laboratory has found that a molecule called CXCR6 is important in directing NKT cells to the liver and lungs. In addition, CXCR6 can regulate the signals that lead to the activation of the anti cancer functions in NKT cells. Consistent with these findings, tumour cells are more likely to spread in mice lacking CXCR6. Dr Johnston?s group will use isolated blood cells and mouse models to study how NKT cells communicate with other cells and how CXCR6 sends signals to activate NKT cells. Other experiments will determine the role of CXCR6 signals in NKT cell development and survival. Finally, Dr Johnston's group will investigate whether CXCR6 and other related molecules can be manipulated to increase NKT cell infiltration into tumours and enhance the elimination of cancer cells. Dr Johnston?s research will allow us to better understand the mechanisms that regulate the activation and localization of NKT cells during cancer responses. The knowledge gained could allow for the development of therapies in which CXCR6 is used to enhance NKT cell infiltration into tumour sites and/or activate NKT cells to direct better responses against tumour cells. Due to the potent ability of NKT cells to prevent the spread of tumour cells to new tissues sites, NKT cell activation could hold promise as a therapy to prevent the spread of cancer cells during surgery or re occurrence of cancers in patients that are in remission.