NKT cell costimulation: experimental progress and therapeutic promise

Trends Mol Med. 2011 Feb;17(2):65-77. doi: 10.1016/j.molmed.2010.10.007. Epub 2010 Nov 17.


Invariant natural killer T (iNKT) cells are innate lymphocytes with unique specificity for glycolipid antigens and remarkable immunomodulatory properties. The role of costimulatory interactions in iNKT cell responses has recently come under scrutiny. Although iNKT 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 iNKT cell-based therapies are far from effective. The concomitant targeting of T cell receptors (TCRs) and costimulatory molecules on iNKT cells represents an exciting new opportunity to optimize such therapeutic approaches. Here, we review recent advances in our understanding of iNKT cell costimulation and discuss potential treatment modalities based on the responsiveness of iNKT cells to disease-tailored glycolipids and select costimulatory ligands.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Immunotherapy*
  • Lymphocyte Activation / immunology
  • Natural Killer T-Cells / immunology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology


  • Antigens, Differentiation
  • Proto-Oncogene Proteins