Therapeutic approaches utilising NKT cells

Natural killer T (NKT) cells are members of the immune armamentarium with profound immunoregulatory effects. They bridge the innate and adaptive immune systems, filling a niche in recognizing glycolipid antigens, and responding rapidly to prime subsequent immune responses. In cancer, type I NKT cells, defined by their semi-invariant T cell receptor (TCR) using V alpha 14J alpha 18 in mice and V alpha 24J alpha 18 in humans, are mostly host protective, by producing interferon-gamma (IFN-gamma) to activate and mature dendritic cells (DC) to make IL-12, which in turn activates NK and CD8(+) T cells. In contrast, type 11 NKT cells, characterized by more diverse TCRs recognizing lipids presented by CD1d, primarily inhibited anti-tumor immunity. This chapter will discuss the impact of CD1d-restricted NKT cells in tumor immune surveillance and immunotherapy and highlight recent therapeutic approaches in tumor mouse models with a focus on harnessing the anti-tumor activities of NKT cells