Differential dendritic cell-mediated activation and functions of invariant NKT-cell subsets in oral cancer

Abstract

Objectives: Invariant natural killer T (iNKT) cells are unique subset of glycolipid-reactive T lymphocytes with potent antitumour characteristics. This study was planned to understand Th-like cytokine profiles of iNKT-cell subsets and modulation of their functions in response to glycolipid ligand and tumour cell lysate (TL).

Subjects and methods: Cytokine profile of iNKT-cell subsets was evaluated from the peripheral blood of eight oral squamous cell carcinoma (OSCC) patients by flow cytometry and enzyme-linked immunosorbent assay (ELISA), while antitumour activity of iNKT cells was measured by methyl tetrazolium salt assay.

Results: CD4(+) (CD4(+) CD8(-)) iNKT subset from OSCC patients showed significant (P < 0.01) expansion and higher IL-4 production following activation with α-GalCer-pulsed DCs, while CD4(-) CD8(-) double negative (DN) and CD8(+) (CD4(-) CD8(+) iNKT subsets produced IFN-γ predominantly. iNKT cells showed significantly (P = 0.02) increased secretion of IFN-γ and enhanced cytotoxicity to KB and SCC-4 tumour cells in response to α-GalCer and TL-pulsed DCs.

Conclusion: It appears that mutual balance/ratio of iNKT subsets may be important for their effector functions. Selectively expanded DN and CD8(+) iNKT cells with α-GalCer and TL may be a better candidate vaccine for iNKT-cell-based adoptive cancer immunotherapy.

Keywords: cytokine; cytotoxicity; dendritic cells; iNKT subsets; oral cancer; α-galactosylceramide.