PMID- 24829411 OWN - NLM STAT- MEDLINE DCOM- 20140818 LR - 20171116 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 192 IP - 12 DP - 2014 Jun 15 TI - Antigen delivery to CD11c+CD8- dendritic cells induces protective immune responses against experimental melanoma in mice in vivo. PG - 5830-8 LID - 10.4049/jimmunol.1300975 [doi] AB - 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. CI - Copyright (c) 2014 by The American Association of Immunologists, Inc. FAU - Neubert, Kirsten AU - Neubert K AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Lehmann, Christian H K AU - Lehmann CH AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Heger, Lukas AU - Heger L AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Baranska, Anna AU - Baranska A AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Staedtler, Anna Maria AU - Staedtler AM AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Buchholz, Veit R AU - Buchholz VR AD - Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; FAU - Yamazaki, Sayuri AU - Yamazaki S AD - Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; FAU - Heidkamp, Gordon F AU - Heidkamp GF AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Eissing, Nathalie AU - Eissing N AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; FAU - Zebroski, Henry AU - Zebroski H AD - Proteomics Resource Center, The Rockefeller University, New York 10065; FAU - Nussenzweig, Michel C AU - Nussenzweig MC AD - Laboratory of Molecular Immunology, The Rockefeller University, New York 10065; and. FAU - Nimmerjahn, Falk AU - Nimmerjahn F AD - Department of Biology, Friedrich-Alexander University Erlangen-Nurnberg, 91058 Erlangen, Germany. FAU - Dudziak, Diana AU - Dudziak D AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander University Erlangen-Nurnberg, University Hospital Erlangen, 91052 Erlangen, Germany; diana.dudziak@uk-erlangen.de. LA - eng GR - Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140514 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antibodies) RN - 0 (Antigens, Neoplasm) RN - 0 (CD11c Antigen) RN - 0 (CD8 Antigens) RN - 0 (Interferon Inducers) RN - 0 (TLR3 protein, mouse) RN - 0 (Toll-Like Receptor 3) RN - O84C90HH2L (Poly I-C) SB - IM MH - Animals MH - Antibodies/pharmacology MH - Antigen Presentation/drug effects/immunology MH - Antigens, Neoplasm/immunology/*pharmacology MH - CD11c Antigen/*immunology MH - CD8 Antigens/*immunology MH - Cell Line, Tumor MH - Dendritic Cells/*immunology/pathology MH - Interferon Inducers/pharmacology MH - Male MH - Melanoma/immunology/pathology/*therapy MH - Mice MH - Neoplasms, Experimental/immunology/pathology/*therapy MH - Poly I-C/pharmacology MH - Toll-Like Receptor 3/agonists/immunology EDAT- 2014/05/16 06:00 MHDA- 2014/08/19 06:00 CRDT- 2014/05/16 06:00 PHST- 2014/05/16 06:00 [entrez] PHST- 2014/05/16 06:00 [pubmed] PHST- 2014/08/19 06:00 [medline] AID - jimmunol.1300975 [pii] AID - 10.4049/jimmunol.1300975 [doi] PST - ppublish SO - J Immunol. 2014 Jun 15;192(12):5830-8. doi: 10.4049/jimmunol.1300975. Epub 2014 May 14.