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[Cancer Research 61, 8643-8646, December 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

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

Julia Steitz, Jürgen Brück, Julia Lenz, Jürgen Knop and Thomas Tüting1

Department of Dermatology, J. Gutenberg University, D-55101 Mainz, Germany

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.




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