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

Type I IFNs, including IFN-alpha, 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-alpha as an adjuvant for...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2009-06, Vol.182 (12), p.7398-7407
Main Authors: Sikora, Andrew G, Jaffarzad, Nina, Hailemichael, Yared, Gelbard, Alexander, Stonier, Spencer W, Schluns, Kimberly S, Frasca, Loredana, Lou, Yanyan, Liu, Chengwen, Andersson, Helen A, Hwu, Patrick, Overwijk, Willem W
Format: Article
Language:English
Subjects:
Animals
Antigens - immunology
Apoptosis - immunology
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell Proliferation
Cells, Cultured
Coculture Techniques
Immunologic Memory - immunology
Immunotherapy
Interferon-alpha - immunology
Interleukin-15 - immunology
Lymphocyte Count
Melanoma - immunology
Melanoma - pathology
Melanoma - therapy
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Phenotype
Receptor, Interferon alpha-beta - immunology
Vaccines, Subunit - immunology
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Summary:Type I IFNs, including IFN-alpha, 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-alpha 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 gp100(25-33) peptide in IFA. IFN-alpha 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-alpha dramatically increased the accumulation of gp100-specific, IFN-gamma-secreting, CD8(+) T cells in the tumor through reduced apoptosis and enhanced proliferation of Ag-specific CD8(+) T cells. IFN-alpha 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-alpha receptor on the T cells and IL-15 in the host. These results demonstrate the efficacy of IFN-alpha 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-alpha therapy for melanoma.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0802982