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Antigen Delivery to CD11c+CD8− Dendritic Cells Induces Protective Immune Responses against Experimental Melanoma in Mice In Vivo
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- Kirsten Neubert
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Christian H K Lehmann
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Lukas Heger
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Anna Baranska
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Anna Maria Staedtler
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Veit R Buchholz
- Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich (TUM) , 81675 Munich,
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- Sayuri Yamazaki
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,
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- Gordon F Heidkamp
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Nathalie Eissing
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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- Henry Zebroski
- Proteomics Resource Center, The Rockefeller University , New York 10065
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- Michel C Nussenzweig
- Laboratory of Molecular Immunology, The Rockefeller University , New York 10065
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- Falk Nimmerjahn
- Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg , 91058 Erlangen,
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- Diana Dudziak
- Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen , 91052 Erlangen,
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Description
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
Journal
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- The Journal of Immunology
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The Journal of Immunology 192 (12), 5830-5838, 2014-06
Oxford University Press (OUP)
