Depletion of CD25(+) CD4(+) T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon alpha-induced, CD8(+) T-cell-dependent immune defense of B16 melanoma.
Transduction of B16 melanoma cells with IFN alpha (B16-IFN alpha) enhances CD8(+) T-cell-dependent tumor immunity in mice, resulting in delayed outgrowth in vivo. Here we provide evidence that CD4(+) T cells down-regulate the IFN alpha-induced tumor immune defense. Importantly, depletion of regulatory CD25(+) CD4(+) T cells prevented growth of B16-IFN alpha in most mice and promoted long-lasting protective tumor immunity. Rejection of B16-IFN alpha could also be achieved with therapeutic injections of dendritic cells genetically engineered to express the melanoma antigen tyrosinase-related protein 2. These results support the development of novel strategies for the immunotherapy of melanoma using IFN alpha in combination with elimination of regulatory T cells or antigen-specific immunization.
Steitz
J
J
Department of Dermatology, J. Gutenberg University, D-55101 Mainz, Germany.
Brück
J
J
Lenz
J
J
Knop
J
J
Tüting
T
T
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology*; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D016898:Interferon-alpha; D015375:Receptors, Interleukin-2; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase