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

Kikuchi, A., Nieda, M., Schmidt, C., Koezuka, Y., Ishihara, S., Ishikawa, Y., Tadokoro, K., Durrant, S., Boyd, A., Juji, T. and Nicol, A. (2001) In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma. British Journal of Cancer, 85 5: 741-746. doi:10.1054/bjoc.2001.1973


Author Kikuchi, A.
Nieda, M.
Schmidt, C.
Koezuka, Y.
Ishihara, S.
Ishikawa, Y.
Tadokoro, K.
Durrant, S.
Boyd, A.
Juji, T.
Nicol, A.
Title In vitro anti-tumour activity of α-galactosylceramide-stimulated human invariant Vα24+NKT cells against melanoma
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1054/bjoc.2001.1973
Open Access Status DOI
Volume 85
Issue 5
Start page 741
End page 746
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract alpha -galactosylceramide (KRN 7000, alpha -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 V alpha 24+NKT-cells. We hypothesized that human V alpha 24+NKT-cells activated by alpha -GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, V alpha 24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with alpha -GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). V alpha 24+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 V alpha 24+NKT-cells (mean +/- SD inhibition of proliferation 63.9 +/- 1.3%). Culture supernatants of activated V alpha 24+NKT-cell cultures stimulated with alpha -GalCer pulsed Mo-DCs exhibited similar anti proliferative 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-gamma, 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 V alpha 24+NKT-cells stimulated by alpha -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 V alpha 24+NKT-cells may contribute to clinical anti-tumour effects of alpha -GalCer. (C) 2001 Cancer Research Campaign.
Keyword Oncology
melanoma
anti-tumour activity
V alpha 24+NKT-cells
alpha-GalCer
IFN-gamma
V(alpha)14 Nkt Cells
T-cells
Antitumor-activity
Dendritic Cells
Il-12
Glycosylceramide
Cytotoxicity
Activation
Expression
Receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Sat, 26 Jan 2008, 01:28:13 EST