NKT cell costimulation: experimental progress and therapeutic promise

Invariant natural killer T ( i NKT) cells are innate lymphocytes with unique specificity for glycolipid antigens and remarkable immunomodulatory properties. The role of costimulatory interactions in i NKT cell responses has recently come under scrutiny. Although i NKT cells and their prototype glycolipid agonist α-galactosylceramide (α-GalCer) have shown promise in several clinical trials conducted in patients with cancer or viral diseases, current i NKT cell-based therapies are far from effective. The concomitant targeting of T cell receptors (TCRs) and costimulatory molecules on i NKT cells represents an exciting new opportunity to optimize such therapeutic approaches. Here, we review recent advances in our understanding of i NKT cell costimulation and discuss potential treatment modalities based on the responsiveness of i NKT cells to disease-tailored glycolipids and select costimulatory ligands.