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

Br J Cancer. 2001 Sep 1;85(5):741-6. doi: 10.1054/bjoc.2001.1973.


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.

MeSH terms

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


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