Interferon-alpha (IFN-α) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC)

IFN-α administration after primary tumour resection improves the survival of melanoma patients at high risk of relapse. To investigate whether this response might be due to stimulation of anti-tumour immunity, the effect of IFN-α on anti-melanoma CTL generation in MLTC was measured. IFN-α increased both allogeneic and autologous anti-melanoma CTL generation from peripheral blood lymphocytes stimulated with irradiated primary melanoma cultures. IFN-α up-regulated MHC class I expression on primary melanoma cultures, whereas IFN-γ up-regulated both MHC class I and II expression. However, the effect of IFN-α on anti-melanoma CTL generation was often more potent than that of IFN-γ, equalling the effect of the optimal combination of IL-2 and IL-12. Pre-treatment of primary melanoma cultures with IFN-γ was sufficient for CTL generation in MLTC, whereas IFN-α needed to be present during the MLTC. While direct anti-proliferative effects of IFN-α on some tumour cells have been described, IFN-α did not inhibit proliferation of primary melanoma cultures. These results suggest that the clinical effects of IFN-α in melanoma patients may be immune-mediated.