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 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.
Sikora
Andrew G
AG
Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jaffarzad
Nina
N
Hailemichael
Yared
Y
Gelbard
Alexander
A
Stonier
Spencer W
SW
Schluns
Kimberly S
KS
Frasca
Loredana
L
Lou
Yanyan
Y
Liu
Chengwen
C
Andersson
Helen A
HA
Hwu
Patrick
P
Overwijk
Willem W
WW
D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy; D016898:Interferon-alpha / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology; D018655:Lymphocyte Count; D008545:Melanoma / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010641:Phenotype; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
D000941:Antigens; D016898:Interferon-alpha; D019409:Interleukin-15; D022223:Vaccines, Subunit; D053633:Receptor, Interferon alpha-beta