IFN-α enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity

Andrew G. Sikora, Nina Jaffarzad, Yared Hailemichael, Alexander Gelbard, Spencer W. Stonier, Kimberly S. Schluns, Loredana Frasca, Yanyan Lou, Chengwen Liu, Helen A. Andersson, Patrick Hwu, Willem W. Overwijk

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Type I IFNs, including IFN-α, enhance Ag presentation and promote the expansion, survival, and effector function of CD8+ CTL during viral infection. Because these are ideal characteristics for a vaccine adjuvant, we examined the efficacy and mechanism of exogenous IFN-α as an adjuvant for antimelanoma peptide vaccination. We studied the expansion of pmel-1 transgenic CD8+ T cells specific for the gp100 melanocyte differentiation Ag after vaccination of mice with gp10025-33 peptide in IFA. IFN-α synergized with peptide vaccination in a dose-dependent manner by boosting relative and absolute numbers of gp100-specific T cells that suppressed B16 melanoma growth. IFN-α dramatically increased the accumulation of gp100-specific, IFN-α-secreting, CD8+ T cells in the tumor through reduced apoptosis and enhanced proliferation of Ag-specific CD8 + T cells. IFN-α treatment also greatly increased the long-term maintenance of pmel-1 CD8+ T cells with an effector memory phenotype, a process that required expression of IFN-α receptor on the T cells and IL-15 in the host. These results demonstrate the efficacy of IFN-α as an adjuvant for peptide vaccination, give insight into its mechanism of action, and provide a rationale for clinical trials in which vaccination is combined with standard-of-care IFN-α therapy for melanoma.

Original languageEnglish (US)
Pages (from-to)7398-7407
Number of pages10
JournalJournal of Immunology
Volume182
Issue number12
DOIs
StatePublished - Jun 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sikora, A. G., Jaffarzad, N., Hailemichael, Y., Gelbard, A., Stonier, S. W., Schluns, K. S., Frasca, L., Lou, Y., Liu, C., Andersson, H. A., Hwu, P., & Overwijk, W. W. (2009). IFN-α enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity. Journal of Immunology, 182(12), 7398-7407. https://doi.org/10.4049/jimmunol.0802982