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

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 gp100_25-33 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.