Abstract

BACKGROUND: Melanoma is among the most aggressive forms of cancer. Our latest retrospective analysis showed that recombinant human interferon-alpha1b (IFN-α1b) led to significantly prolonged survival with mild toxicity in patients with stage IV melanoma. Based on this clinical finding, the current study sought to investigate the influence of IFN-α1b on the antitumor immunity of melanoma, with interferon-alpha2b (IFN-α2b) used as a control.

MATERIAL AND METHODS: Peripheral blood mononuclear cells were stimulated with culture medium alone, or medium supplemented with IFN-α1b or IFN-α2b. Flow cytometry and lactate dehydrogenase release assays were used to evaluate cytotoxic effects. Flow cytometry and enzyme-linked immunospot assays were used to analyze immunoregulatory effects on natural killer (NK) cells, natural killer T (NKT) cells, CD3⁺CD8⁺ T cells, and melanoma cells. Cell Counting Kit-8 assay was performed to measure the effect on proliferation of melanoma cells in vitro.

RESULTS: IFN-α1b enhanced the activity of NK cells, NKT cells, and CD3⁺CD8⁺ T cells from melanoma patients. Compared with IFN-α2b, IFN-α1b induced a relatively lower level of programmed cell death-ligand 1 (PD-L1) in melanoma cells without affecting the expression of PD-L1 in CD3⁺CD8⁺ T cells. Additionally, IFN-α1b showed a much stronger inhibition of the proliferation of melanoma cells than IFN-α2b.

CONCLUSIONS: IFN-α1b has an immunostimulatory activity similar to IFN-α2b and possesses milder adverse effects on immune checkpoints and stronger inhibitory effects on melanoma cell growth than IFN-α2b. Therefore, IFN-α1b is a promising drug for the treatment of melanoma.

Keywords: Antigens, CD274, Immunomodulation, Interferon-alpha, Melanoma, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Apoptosis, CD8-Positive T-Lymphocytes, Cell Proliferation, Immunity, Interferon alpha-2, interferon-gamma, Leukocytes, Mononuclear, Lymphocyte Activation, Middle Aged, Natural Killer T-Cells