Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells

J Clin Immunol. 2012 Oct;32(5):1071-81. doi: 10.1007/s10875-012-9697-9. Epub 2012 Apr 26.


Purpose: 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.

Conclusion: The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy
  • Aged
  • Antigen-Presenting Cells / immunology*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / therapy
  • Galactosylceramides*
  • Humans
  • Immunotherapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Lymph Nodes / immunology
  • Male
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Tumor Microenvironment / immunology


  • Galactosylceramides
  • Receptors, Antigen, T-Cell
  • Valpha24 protein, human
  • alpha-galactosylceramide