Invariant natural killer T cells and immunotherapy of cancer

Invariant CD1d restricted natural killer T (iNKT) cells are regulatory cells that express a canonical TCR-V alpha-chain (V alpha 24.J alpha 18 in humans and V alpha 14.J alpha 18 in mice) which recognizes glycolipid antigens presented by the monomorphic CD1d molecule. They can secrete a wide variety of both pro-inflammatory and anti-inflammatory cytokines very swiftly upon their activation. Evidence for the significance of iNKT cells in human cancer has been ambiguous. Stilt, the (pre-)clinical findings reviewed here, provide evidence for a distinct contribution of iNKT cells to natural anti-tumor immune responses in humans. Furthermore, clinical phase I studies that are discussed here have revealed that the infusion of cancer patients with ligand-loaded dendritic cells or cultured iNKT cells is well tolerated. We thus underscore the potential of iNKT cell based immunotherapy in conjunction with established modalities such as surgery and radiotherapy, as adjuvant therapy against carcinomas. (C) 2008 Elsevier Inc. All rights reserved.