title: Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion.
abstract: Brain tumors carry a poor prognosis, and newer approaches to their therapy are urgently needed. Natural killer T (NKT) cells are distinct innate lymphocytes with antitumor potentials. Defects in NKT cell function have been observed in patients with other forms of cancer. Here we show that both the frequency and interferon-gamma-producing function of NKT cells are well preserved in adult patients with glioma (n=9) and comparable to findings in healthy controls (n=9). These cells can be readily expanded in culture using autologous mature dendritic cells loaded with the NKT ligand, alpha-galactosyl ceramide. The expanded NKT cells from glioma patients are functional and, importantly, kill glioma cells in a ligand- and CD1d-dependent manner. Expression of CD1d is detected both on primary glioma cells as well as endothelial cells in infiltrating new blood vessels by immunohistochemistry of glioma tissue sections. These data suggest that targeting NKT cells may provide a novel strategy for immunotherapy of glioma.
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Human Disease, Rockefeller University, New York, NY 10021, USA.
authors.forename: Kavita M
authors.initials: KM
authors.lastname: Dhodapkar
authors.forename: Barbara
authors.initials: B
authors.lastname: Cirignano
authors.forename: Francesca
authors.initials: F
authors.lastname: Chamian
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D008024:Ligands; D007371:Interferon-gamma