Project 467212

Invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells are unique subsets of T cells that have been shown to be involved in regulating immune responses to tumors and microbes. Upon their activation, iNKT and MAIT cells can secrete large amounts of inflammatory mediators that allow them to regulate a variety of other immune cells, including B cells, natural killer cells, and macrophages. However, whether and how activated iNKT and MAIT cells regulate each other remains unknown. Therefore, we aim to investigate the presence of a cross-talk between these cells in a mouse model. To do so, we will use flow cytometry to assess the activation of MAIT cells following iNKT cell activation, and vice versa. Activation will be measured through the presence of activation markers on the cell's surface as well as the cell's ability to produce inflammatory mediators, also known as cytokines. Then, we aim to discover the effect of this iNKT-MAIT cell cross-talk in a mouse tumor model, namely the B16 pulmonary melanoma metastases model. Overall, iNKT and MAIT cells are attractive therapeutic targets because drugs that activate them should work uniformly across genetically diverse individuals. So far, drugs that activate iNKT cells have been used in clinical trials for the treatment of cancers and viral diseases, such as chronic hepatitis B. Additionally, MAIT cells have been shown to produce immune responses that can either inhibit or promote tumor growth. Therefore, understanding the interaction that may occur between iNKT and MAIT cells could have important implications for the optimization and combination of future immunotherapies.