Complementary approaches to study NKT cells in cancer

NKT cells are a small but influential member of the T cell family, recognizing lipids presented by the non-classical MHC-like molecule CD1d rather than peptides presented by classical MHC molecules. They bridge between the innate and adaptive immune systems, serving as rapid responders but also allowing the T cell immune system to recognize lipid antigens, for example derived from tumors or bacteria. They also serve as potent regulatory cells, controlling other immune responses. Type I NKT cells use a semi-invariant T cell receptor (TCR) whereas type II use diverse TCRs. Most often, type I NKT cells promote tumor immunity whereas type II tend to suppress it, and the two subtypes crossregulate each other, forming an immunoregulatory axis. Lack of tools to study these important cells has limited the understanding of these, but newer tools have allowed great advances, especially in mouse models. These range from transgenic and knock-out mice to CD1d tetramers carrying ligands for type I or II NKT cells, to antibodies and NKT cell hybridomas. Here we describe these complementary tools and approaches and their use to study NKT cells and their role in the immunology and immunotherapy of cancer.