In vitro anti-tumour activity of alpha-galactosylceramide-stimulated human invariant Valpha24+NKT cells against melanoma.

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 Valpha24+NKT-cells. We hypothesized that human Valpha24+NKT-cells activated by alpha-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Valpha24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with alpha-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Valpha24+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 Valpha24+NKT-cells (mean +/- SD inhibition of proliferation 63.9 +/- 1.3%). Culture supernatants of activated Valpha24+NKT-cell cultures stimulated with alpha-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-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 Valpha24+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 Valpha24+NKT-cells may contribute to clinical anti-tumour effects of alpha-GalCer.

• Authors: A Kikuchi, M Nieda, C Schmidt, Y Koezuka, S Ishihara, Y Ishikawa, K Tadokoro, S Durrant, A Boyd, T Juji, A Nicol
• Journal: British journal of cancer (Br J Cancer) Vol. 85 Issue 5 Pg. 741-6 (Sep 01 2001) ISSN: 0007-0920 [Print] England
• PMID: 11531261 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Cancer Research Campaign.

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents
• Galactosylceramides
• Interleukin-10
• Interleukin-12
• Interleukin-4
• Interferon-gamma
• KRN 7000

Topics

• Adjuvants, Immunologic (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Division
• Galactosylceramides (pharmacology)
• Humans
• Immunity, Cellular
• Immunotherapy (methods)
• Interferon-gamma (metabolism)
• Interleukin-10 (metabolism, therapeutic use)
• Interleukin-12 (metabolism, therapeutic use)
• Interleukin-4 (metabolism, therapeutic use)
• Killer Cells, Natural (cytology, drug effects, immunology)
• Lymphocyte Activation
• Melanoma (immunology, pathology, therapy)
• Phenotype
• Tumor Cells, Cultured (drug effects)