Accumulation of Activated Invariant Natural Killer T Cells in the Tumor Microenvironment after α-Galactosylceramide-Pulsed Antigen Presenting Cells

The intravenous administration of alpha-Galactosylceramide (alpha-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-gamma 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 alpha-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site. Patients with operable advanced lung cancer received an intravenous injection of alpha-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. Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-gamma production by the alpha-GalCer-stimulated TILs. The administration of alpha-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.