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

The ability of the body's immune system to recognize and destroy abnormal or cancerous cells depends on the proper localization and function of each component. Natural Killer T (NKT) cells are a population of white blood cells that have been shown to induce potent anti-tumour responses and prevent the spread of cancer cells. The infiltration of NKT cells into tumours has been associated with greater survival in patients with certain cancers, while reduced NKT cell numbers in the blood have been associated with poor outcomes. However, the mechanisms that regulate the development, localization and activation of NKT cells are not well understood. One class of molecules that could regulate the tissue distribution and activation of NKT cells are the chemokine receptors. These molecules belong to a family of proteins that have been shown to direct different types of white blood cells to specific locations in the body. We have found that one of these proteins, CXCR6, is expressed on NKT cells and mediates accumulation of NKT cells in the liver and lungs. However, CXCR6 also seems to be important for NKT cell development and activation. NKT cells in mice lacking this protein do not generate normal levels of anti-cancer molecules and are more susceptible to the spread of cancer cells. In this study, we will examine the role that CXCR6 plays in NKT cell development. We will also examine the role that CXCR6 and other chemokine receptors play in NKT cell infiltration into tumours, and how they regulate activation of tumour responses by NKT cells. We will use this knowledge to try to direct NKT cells to cancerous tissues sites more efficiently, and/or activate NKT cells to make better responses to tumour cells. Any potential therapy that can be developed to reduce the burden of cancer will be an important addition to our current arsenal of treatments.