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Published on: April 18, 2016
Differential dendritic cell-mediated activation and functions of invariant NKT-cell subsets in oral cancer
A K Singh1, P Gaur, N K Shukla
1Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
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.
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