Clinical application of NKT cell immune system for lung cancer

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We performed αGalactosylceramide-pulsed Dendritic cells in patients with lung cancer. Patients with advanced non-small cell lung cancer or recurrent lung cancer received intravenous injections of αGalCer-pulsed DCs (1x10^9/m^2) to test the safety, feasibility, and clinical response. Immunomonitoring was also performed in all completed cases. Eligible patients underwent peripheral blood leukapheresis, and peripheral blood mononuclear cells (PBMCs) were collected and further separated by density gradient centrifugation. PBMCs were cultured with human granulocyte-macrophage colony-stimulate factor (GM-CSF) for 1-2 weeks and pulsed with specific ligand, α-Galactosylceramide on the day before administration.Seventeen patients were enrolled in this study. The frequency of peripheral blood NKT cells in all patients was measured by FACS analysis and IFN-γ production after restimulation with αGalCer in PBMCs was measured by ELISPOT assay. Patients with marked increase of FN-γ production following the administration of αGalCer-pulsed DC showed relatively long survival and time to tumor progression, while poor responder of IFN-γ production showed very poor prognosis. This is the first report to show the crucial role of IFN-γ at NKT cell immunotherapy. With these results, the role and mechanisms of IFN-γ production and anti-tumor immune response will be discussed.