Interferon-alpha (IFN-alpha) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC).
IFN-alpha 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-alpha on anti-melanoma CTL generation in MLTC was measured. IFN-alpha increased both allogeneic and autologous anti-melanoma CTL generation from peripheral blood lymphocytes stimulated with irradiated primary melanoma cultures. IFN-alpha up-regulated MHC class I expression on primary melanoma cultures, whereas IFN-gamma up-regulated both MHC class I and II expression. However, the effect of IFN-alpha on anti-melanoma CTL generation was often more potent than that of IFN-gamma, equalling the effect of the optimal combination of IL-2 and IL-12. Pre-treatment of primary melanoma cultures with IFN-gamma was sufficient for CTL generation in MLTC, whereas IFN-alpha needed to be present during the MLTC. While direct anti-proliferative effects of IFN-alpha on some tumour cells have been described, IFN-alpha did not inhibit proliferation of primary melanoma cultures. These results suggest that the clinical effects of IFN-alpha in melanoma patients may be immune-mediated.
Palmer
K J
KJ
Department of Immunology, University College London, Windeyer Institute of Medical Science, and Skin and Melanoma Unit, The Royal Marsden Hospital, London, UK.
Harries
M
M
Gore
M E
ME
Collins
M K
MK
D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000494:pharmacology*; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D007155:Immunologic Factors; D016898:Interferon-alpha