Immunomodulatory effects of high‐dose and low‐dose interferon α2b in patients with high‐risk resected melanoma

Abstract

BACKGROUND The clinical antitumor activity of recombinant interferon α2b (IFNα2b) has been well documented in patients with advanced and high‐risk melanoma; however, its mechanism of action remains conjectural. Trial E2690 evaluated the immunomodulatory effects of IFNα2b in vivo during treatment at high doses (the HDI arm; n = 51 patients) and at low doses (the LDI arm; n = 54 patients) in relation to standard observation (OBS; n = 43 patients). METHODS This study evaluated peripheral blood lymphocytes (PBLs) for phenotypic markers and cytotoxic functions at 1 month, 3 months, and 12 months in the HDI arm, the LDI arm, and the OBS arm and examined correlations between changes observed in PBLs or in tumors with regard to treatment dosage and disease outcome. Tumor biopsy samples were studied for response to IFNα2b at a range of concentrations in vitro. RESULTS Baseline blood phenotypic and functional assays did not predict disease outcome; however, modulation of these immunologic assays by IFNα2b treatment was observed and was associated with IFNα2b dosage. Tumor cell class II major histocompatibility antigen expression (human leukocyte/lymphocyte antigen DR) and adhesion molecule expression (ICAM‐1) were modulated by exposure to IFNα2b in a dose dependent manner. Blood natural killer (NK) cell function, T‐cell function, and subset distribution were modulated early by patients in the HDI arm and later by patients in the LDI arm. None of the variables tested in these studies predicted recurrence free survival. The numbers of patients studied were smaller than may be needed to detect potentially clinically significant changes. CONCLUSIONS These data demonstrate changes in immunologic parameters associated with IFNα2b treatment and dosage that may account for some of the differences in the clinical efficacy of this modality. The current results also suggest the need for further study of newer molecular intermediates of IFNα2b and T‐cell response to specific antigens of melanoma. Cancer 2002;95:1101–12. © 2002 American Cancer Society. DOI 10.1002/cncr.10775