Immunomodulatory function of interferon-gamma in patients with metastatic melanoma: Results of a phase II-B trial in subjects with metastatic melanoma, ecog study E 4987

John M. Kirkwood, John Bryant, Joan H. Schiller, Martin M. Oken, Ernest C. Borden, Theresa L. Whiteside

Research output: Contribution to journalArticle

23 Scopus citations


Interferon-gamma (IFN-γ) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-γ in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-γ (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-γ therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001, on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses ≥0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN-γ reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-γ has been shown to have significant effects on the T-cell compartment of the immune system.

Original languageEnglish (US)
Pages (from-to)146-157
Number of pages12
JournalJournal of Immunotherapy
Issue number2
StatePublished - Jan 1 1997



  • ECOG study
  • IFN-γ
  • Immunomodulation
  • Metastatic melanoma
  • Phase II-B

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this