In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma

Abstract

α-galactosylceramide (KRN 7000, α-GalCer) has shown potent in vivo anti-tumour activity in mice, including against melanoma and the highly specific effect of inducing proliferation and activation of human Vα24+NKT-cells. We hypothesized that human Vα24+NKT-cells activated by α-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Vα24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with α-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Vα24+NKT-cells did not exhibit cytolytic activity against the primary autologous or allogeneic melanoma cell lines tested. However, proliferation of the melanoma cell lines was markedly suppressed by co-culture with activated Vα24+NKT-cells (mean ± SD inhibition of proliferation 63.9 ± 1.3%). Culture supernatants of activated Vα24+NKT-cell cultures stimulated with α-GalCer pulsed Mo-DCs exhibited similar antiproliferative activities against melanoma cells, indicating that the majority of the inhibitory effects were due to soluble mediators rather than direct cell-to-cell interactions. This effect was predominantly due to release of IFN-γ, and to a lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but these cytokines had less antiproliferative effects. These in vitro results show that Vα24+NKT-cells stimulated by α-GalCer-pulsed Mo-DCs have anti-tumour activities against human melanoma through antiproliferative effects exerted by soluble mediators rather than cytolytic effects as observed against some other tumours. Induction of local cytokine release by activated Vα24+NKT-cells may contribute to clinical anti-tumour effects of α-GalCer. © 2001 Cancer Research Campaign www.bjcancer.com

DOI: 10.1054/bjoc.2001.1973

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@article{Kikuchi2001InVA, title={In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma}, author={A Kikuchi and Mie Nieda and Christy Schmidt and Yasuhiko Koezuka and Satoshi Ishihara and Yukio Ishikawa and Kenji Tadokoro and Steve Durrant and Ashleigh Susan Boyd and Takeo Juji and Andrew John Nicol}, journal={British Journal of Cancer}, year={2001}, volume={85}, pages={741 - 746} }