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

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.