| Author |
Nussenzweig, Michel C. Eissing, Nathalie Neubert, Kirsten Lehmann, Christian H. K. Baranska, Anna Staedtler, Anna Maria Yamazaki, Sayuri Dudziak, Diana Buchholz, Veit R. Nimmerjahn, Falk Heger, Lukas Heidkamp, Gordon F. Zebroski, Henry |
| Description |
Author Affiliation: Neubert K ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Lehmann CH ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Heger L ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Baranska A ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Staedtler AM ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Buchholz VR ( Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany); Yamazaki S ( Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan); Heidkamp GF ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Eissing N ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany); Zebroski H ( Proteomics Resource Center, The Rockefeller University, New York 10065); Nussenzweig MC ( Laboratory of Molecular Immunology, The Rockefeller University, New York 10065); Nimmerjahn F ( Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany.); Dudziak D ( Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany) |
| Abstract |
Dendritic cells (DCs) are central modulators of immune responses and, therefore, interesting target cells for the induction of antitumor immune responses. Ag delivery to select DC subpopulations via targeting Abs to DC inhibitory receptor 2 (DCIR2, clone 33D1) or to DEC205 was shown to direct Ags specifically to CD11c(+)CD8(-) or CD11c(+)CD8(+) DCs, respectively, in vivo. In contrast to the increasing knowledge about the induction of immune responses by efficiently cross-presenting CD11c(+)CD8(+) DCs, little is known about the functional role of Ag-presenting CD11c(+)CD8(-) DCs with regard to the initiation of protective immune responses. In this study, we demonstrate that Ag targeting to the CD11c(+)CD8(-) DC subpopulation in the presence of stimulating anti-CD40 Ab and TLR3 ligand polyinosinic-polycytidylic acid induces protective responses against rapidly growing tumor cells in naive animals under preventive and therapeutic treatment regimens in vivo. Of note, this immunization protocol induced a mixed Th1/Th2-driven immune response, irrespective of which DC subpopulation initially presented the Ag. Our results provide important information about the role of CD11c(+)CD8(-) DCs, which have been considered to be less efficient at cross-presenting Ags, in the induction of protective antitumor immune responses. |
