Altered invariant natural killer T cell subsets and its functions in patients with oral squamous cell carcinoma.

Invariant natural killer T (iNKT) cells are glycolipid-reactive T lymphocytes that share receptors and function with natural killer (NK) cells and reportedly play a pivotal role in various immune responses. However, iNKT cells are not well characterized in patients with oral squamous cell carcinoma (OSCC). We investigated the populations and functions of circulating iNKT (CD3(+) 6B11(+) ) cells from thirty-eight patients with OSCC and twenty-eight healthy donors by flow cytometry. Circulating iNKT cells were significantly lower (P < 0.01) in patients as compared to those in healthy controls. Further, iNKT subsets revealed a marked decrease in CD4(-) CD8(-) (double negative, DN) subset with concomitant increase in CD8(+) subset in patients as compared to healthy controls (P = 0.03 and P < 0.01, respectively), whereas CD4(+) subset was similarly distributed in both groups. The functional analysis demonstrated that residual iNKT cells from patients had impaired proliferative response to α-galactosylceramide (α-GalCer)-pulsed dendritic cells (DCs) and Th2-like cytokine profile. However, in vitro activation with α-GalCer-pulsed DCs restores IFN-γ expression and enhances antitumour activity to human cancer cells lines (SCC-4, KB and MCF7). It appears that the selectively enriched iNKT subsets and modulation of their function by specific ligand/agonist may be useful for cellular therapy in patients with OSCC. Further, reduced levels of iNKT cells and its DN subset may be used as potential prognostic factors for patients with OSCC.