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

Sikora AG, Jaffarzad N, Hailemichael Y, Gelbard A, Stonier SW, Schluns KS, Frasca L, Lou Y, Liu C, Andersson HA, Hwu P, Overwijk WW
J Immunol. 2009 182 (12): 7398-407

PMID: 19494262 · PMCID: PMC2774140 · DOI:10.4049/jimmunol.0802982

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.

MeSH Terms (19)

Animals Antigens Apoptosis CD8-Positive T-Lymphocytes Cell Proliferation Cells, Cultured Coculture Techniques Immunologic Memory Immunotherapy Interferon-alpha Interleukin-15 Lymphocyte Count Melanoma Mice Mice, Inbred C57BL Neoplasm Transplantation Phenotype Receptor, Interferon alpha-beta Vaccines, Subunit

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