Pattern of restoration of the immune alterations by the treatment with high doses of Interferon alpha in high risk melanoma patients

Abstract

7534 Background: IFNa is currently use in the adjuvant treatment of patients with high risk of melanoma. The mechanism of action of IFNa is complex. Since it, IFNa is able to modulate different regulatory and effectors cells of the immune system. Therefore, the optimization of the clinical use of IFNa requires the analysis of the biological effects of the biotherapy. Herein, we have investigated the effects of high doses of IFNa in the expression of chemokine receptors by peripheral blood (PB) lymphocytes and the spontaneous cytotoxic (NK) activity of PB mononuclear cells (PBMC) in patients with high risk melanoma. Methods: 15 patients with melanoma stage III were treated with intravenous IFNa 20MU/m2 5 days per week for 4 weeks follow by intramuscular IFNa 10 MU/m2 3 days per weeks for 48 weeks. PBMC were obtained by venous puncture before the first dose of IFNa, every last day of the first 4 weeks of treatment, and at 3, 6, 9 and 12 months of the maintenance treatment. The expression of differentiation antigens and chemokine receptors were measured by direct surface immunofluorescence and flowcytometry. NK activity was measured by 51Cr release assay using as targets K562 cells. 15 age and sex matched healthy donors were use as controls. Results: Before the biotherapy, melanoma patients showed significantly reduced expression of CXCR4 and CCR2 on the surface of CD19+ B cells (P<0.05), as well as reduced CXCR4+CD3+ T cells and CD16+CD3- NK cells (P<0.05). The expression of CXCR4 by B, T and NK cells was normalized, as compared to controls, after 4 weeks of treatment. The normalization of the expression of CCR2 in the latter lymphocyte subsets was achieved only after 3 months of treatment. NK cytotoxic activity in PBMC remained significant decreased during the first 9 months but normalization occurred after 12 months of treatment. Conclusions: This study demonstrates that high doses of IFNa promote clear immunomodulatory effects in high risk melanoma patients. Notably, the normalization of immunological parameters is sequential and beneficial accumulative effects are evident after 9 months which provides a rational to recommend maintenance therapy. No significant financial relationships to disclose.