title: Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells.
abstract: OBJECTIVE
  The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site.
  
  
  METHODS
  Patients with operable advanced lung cancer received an intravenous injection of α-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed.
  
  
  RESULTS
  Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs.
  
  
  CONCLUSIONS
  The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Clinical Research Center, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nagato
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ishibashi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Okita
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Moriya
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Hoshino
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Hideki
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Fujii
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D005699:Galactosylceramides; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D005699:Galactosylceramides; D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human; C493154:alpha-galactosylceramide