Application of natural killer T cells in antitumor immunotherapy

NKT cells are a unique subset of T cells that recognize glycolipid antigens presented by CD1d molecules. NKT cells have the potential to produce key cytokines of both Th1 and Th2 T cells and are involved in the control of several types of immune response. Furthermore, NKT cells perform spontaneous tumor immunosurveillance. Upon specific activation with alpha-GalCer, NKT cells show strong antitumor immune responses through direct cytotoxicity and indirect activation of a cascade of antitumor effector cells such as natural killer (NK) cells and CD8+ cytotoxic T cells. In addition to alpha-GalCer, many other CD1d ligands, including self and bacterial glycolipids and modified synthetic glycolipid antigens, have also been discovered. Structurally different glycolipid antigens have the distinct ability to activate NKT cells. Thus, it seems that we are now close to a position in which we can control the activation status of NKT cells; this makes NKT cells an ideal target of anticancer immunotherapies. Clinical trials with soluble alpha-GalCer or alpha-GalCer-pulsed dendritic cells aimed at in vivo reconstitution and activation of human NKT cells have provided both promising and challenging results. In this review, we discuss NKT-cell-mediated antitumor immune responses, as well as the early outcomes and implications of recent clinical studies.