Antigen delivery to CD11c+CD8- dendritic cells induces protective immune responses against experimental melanoma in mice in vivo.
Kirsten Neubert,Christian H. K. Lehmann,Lukas Heger,Anna Baranska,Anna Maria Staedtler,Veit R. Buchholz,Sayuri Yamazaki,Gordon F. Heidkamp,Nathalie Eissing,Henry Zebroski,Michel C. Nussenzweig,Falk Nimmerjahn,Diana Dudziak +12 more
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TLDR
It is demonstrated 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.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.read more
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Journal ArticleDOI
Transcriptional Control of Dendritic Cell Development
Theresa L. Murphy,Gary E. Grajales-Reyes,Xiaodi Wu,Roxane Tussiwand,Carlos G. Briseño,Arifumi Iwata,Nicole M. Kretzer,Vivek Durai,Kenneth M. Murphy +8 more
TL;DR: This work has assigned several nonredundant in vivo functions to distinct DC lineages, consisting of plasmacytoid DCs and several subsets of classical DCs that promote different immune effector modules in response to pathogens.
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Dendritic cells for cancer immunotherapy
TL;DR: New insights facilitate the direct targeting of antigens to DC surface receptors in vivo rather than ex vivo culturing DC and antigen loading and novel DC immunotherapies will be in combination with drugs targeting immunological check points.
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Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor Immunity and How
TL;DR: Basic research and clinical data supporting the hypothesis that the protective antitumor functions of cDC1 inferred from mouse preclinical models are conserved in humans are summarized and discussed.
Book ChapterDOI
Cross-Presentation in Mouse and Human Dendritic Cells.
TL;DR: This chapter discusses recent advances in the understanding of the molecular mechanisms of cross-presentation, and describes the different DC subsets identified in mouse and human, and their functional specialization for cross- presentation.
Journal ArticleDOI
CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion.
Lukas Heger,Silke Balk,Jennifer J. Lühr,Gordon F. Heidkamp,Christian H. K. Lehmann,Lukas Hatscher,Ariawan Purbojo,Arndt Hartmann,Fayna Garcia-Martin,Shin-Ichiro Nishimura,Robert Cesnjevar,Falk Nimmerjahn,Diana Dudziak +12 more
TL;DR: CLEC10A represents not only a candidate to better define CD1c+ DCs—due to its high endocytic potential—but also exhibits an interesting candidate receptor for future antigen-targeting approaches.
References
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TL;DR: Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis and the realization that these cells are a powerful tool for manipulating the immune system is realized.
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Taro Kawai,Shizuo Akira +1 more
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Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.
Frank O. Nestle,Selma Alijagic,Michel Gilliet,Yuansheng Sun,Stephan Grabbe,Reinhard Dummer,Günter Burg,Dirk Schadendorf +7 more
TL;DR: Vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma and antigen-specific immunity was induced during DC vaccination.
Journal ArticleDOI
Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
Journal ArticleDOI
Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo
Daniel Hawiger,Kayo Inaba,Kayo Inaba,Yair Dorsett,Ming Guo,Karsten Mahnke,Miguel Rivera,Jeffrey V. Ravetch,Ralph M. Steinman,Michel C. Nussenzweig,Michel C. Nussenzweig +10 more
TL;DR: An antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor is devised, which concludes that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.