Harnessing CD1d-restricted T cells toward antitumor immunity in humans.
Natural killer T (NKT) cells are a distinct subset of T cells that recognize lipid antigens in the context of CD1d molecules. There is a considerable body of evidence implicating a role for NKT cells in regulating antitumor immunity in mice. alpha-Galactosylceramide (alpha-GalCer) is a potent agonist ligand for type I NKT cells. We and others have shown that injection of alpha-GalCer-loaded dendritic cells leads to clear expansion of NKT cells in vivo in cancer patients. Preclinical studies suggest the capacity of thalidomide analogues to enhance ligand-dependent NKT activation and provide the rationale for combination approaches that are now being designed. Recently, we demonstrated the presence of CD1d-restricted T cells specific for an inflammation-associated lipid, lysophosphatidylcholine, in patients with advanced myeloma. These studies suggest that type II NKT cells may play a role in sensing and regulating inflammation. Harnessing CD1d-restricted T cells in cancer may depend on regulating the balance between type I and II NKT cells and holds promise as a broad strategy for immune therapy of several cancers.
Neparidze
Natalia
N
Section of Hematology, Yale University, New Haven, CT 06510, USA.
Dhodapkar
Madhav V
MV
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D055610:Antigens, CD1d / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007109:Immunity; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000276:immunology; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta