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

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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 withα-GalCer-pulsed DCs, while CD4−CD8− double negative (DN) and CD8+ (CD4−CD8+) iNKT subsets produced IFN-γpredominantly. iNKT cells showed significantly (P= 0.02) increased secretion of IFN-γand enhanced cytotoxicity to KB and SCC-4 tumour cells in response toα-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 withα-GalCer and TL may be a better candidate vaccine for iNKT-cell-based adoptive cancer immunotherapy.

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