Antigen delivery to CD11c+CD8- dendritic cells induces protective immune responses against experimental melanoma in mice in vivo.
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.
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Kirsten
K
Neubert
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Christian H K
CH
Lehmann
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Lukas
L
Heger
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Anna
A
Baranska
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Anna Maria
AM
Staedtler
Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany;
Veit R
VR
Buchholz
Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;
Sayuri
S
Yamazaki
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Gordon F
GF
Heidkamp
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany;
Nathalie
N
Eissing
Proteomics Resource Center, The Rockefeller University, New York 10065;
Henry
H
Zebroski
Laboratory of Molecular Immunology, The Rockefeller University, New York 10065; and.
Michel C
MC
Nussenzweig
Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany.
Falk
F
Nimmerjahn
Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91052 Erlangen, Germany; diana.dudziak@uk-erlangen.de.
Diana
D
Dudziak
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000494:pharmacology*; D039521:CD11c Antigen / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D007369:Interferon Inducers / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011070:Poly I-C / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology
D000906:Antibodies; D000951:Antigens, Neoplasm; D039521:CD11c Antigen; D016827:CD8 Antigens; D007369:Interferon Inducers; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D011070:Poly I-C