NKT Cells in Tumor Immunity

Abstract

NKT cells are a small subset of true T cells that bridge between the innate and adaptive immune systems, provide the cellular immune system with a means to recognize lipid antigens, and interact with and regulate other parts of the immune system. In particular, they regulate tumor immunity both positively and negatively. They are defined by their recognition of lipid antigens presented by the nonclassical MHC molecule CD1d, rather than conventional MHC class I or II molecules. Classical or type I NKT cells use a semi-invariant T cell receptor with a conserved alpha chain in both mice and humans, recognize alpha-galactosylceramide and its homologues, and generally promote tumor immunity. Type II NKT cells use diverse receptors, recognize other lipids such as sulfatide, and usually suppress tumor immunity. These two subsets also cross-regulate each other and influence other immunoregulatory cells. The balance along the axis between type I and type II NKT cells can have profound effects on both innate and adaptive tumor immunosurveillance and tumor immunity, as well as vaccine responses. Harnessing these cells to fight cancer is being undertaken in clinical trials and is beginning to show promise.