Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential
Dendritic cells (DCs) are the quintessential antigen-presenting cells of the human immune system and play a prime role in coordinating innate and adaptive immune responses, explaining the strong and still growing interest in their application for cancer immunotherapy. Much current research in the fi...
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| Veröffentlicht in: | PloS one 2012-12, Vol.7 (12), p.e51851 |
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| creator | Anguille, Sébastien Lion, Eva Tel, Jurjen de Vries, I Jolanda M Couderé, Karen Fromm, Phillip D Van Tendeloo, Viggo F Smits, Evelien L Berneman, Zwi N |
| description | Dendritic cells (DCs) are the quintessential antigen-presenting cells of the human immune system and play a prime role in coordinating innate and adaptive immune responses, explaining the strong and still growing interest in their application for cancer immunotherapy. Much current research in the field of DC-based immunotherapy focuses on optimizing the culture conditions for in vitro DC generation in order to assure that DCs with the best possible immunogenic qualities are being used for immunotherapy. In this context, monocyte-derived DCs that are alternatively induced by interleukin-15 (IL-15 DCs) have attracted recent attention due to their superior immunostimulatory characteristics. In this study, we show that IL-15 DCs, in addition to potent tumor antigen-presenting function, possess tumoricidal potential and thus qualify for the designation of killer DCs. Notwithstanding marked expression of the natural killer (NK) cell marker CD56 on a subset of IL-15 DCs, we found no evidence of a further phenotypic overlap between IL-15 DCs and NK cells. Allostimulation and antigen presentation assays confirmed that IL-15 DCs should be regarded as bona fide myeloid DCs not only from the phenotypic but also from the functional point of view. Concerning their cytotoxic activity, we demonstrate that IL-15 DCs are able to induce apoptotic cell death of the human K562 tumor cell line, while sparing tumor antigen-specific T cells. The cytotoxicity of IL-15 DCs is predominantly mediated by granzyme B and, to a small extent, by tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, Fas ligand and TNF-α. In conclusion, our data provide evidence of a previously unappreciated role for IL-15 in the differentiation of human monocytes towards killer DCs. The observation that IL-15 DCs have killer DC capacity lends further support to their implementation in DC-based immunotherapy protocols. |
| doi_str_mv | 10.1371/journal.pone.0051851 |
| format | Article |
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Much current research in the field of DC-based immunotherapy focuses on optimizing the culture conditions for in vitro DC generation in order to assure that DCs with the best possible immunogenic qualities are being used for immunotherapy. In this context, monocyte-derived DCs that are alternatively induced by interleukin-15 (IL-15 DCs) have attracted recent attention due to their superior immunostimulatory characteristics. In this study, we show that IL-15 DCs, in addition to potent tumor antigen-presenting function, possess tumoricidal potential and thus qualify for the designation of killer DCs. Notwithstanding marked expression of the natural killer (NK) cell marker CD56 on a subset of IL-15 DCs, we found no evidence of a further phenotypic overlap between IL-15 DCs and NK cells. Allostimulation and antigen presentation assays confirmed that IL-15 DCs should be regarded as bona fide myeloid DCs not only from the phenotypic but also from the functional point of view. Concerning their cytotoxic activity, we demonstrate that IL-15 DCs are able to induce apoptotic cell death of the human K562 tumor cell line, while sparing tumor antigen-specific T cells. The cytotoxicity of IL-15 DCs is predominantly mediated by granzyme B and, to a small extent, by tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, Fas ligand and TNF-α. In conclusion, our data provide evidence of a previously unappreciated role for IL-15 in the differentiation of human monocytes towards killer DCs. The observation that IL-15 DCs have killer DC capacity lends further support to their implementation in DC-based immunotherapy protocols.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051851</identifier><identifier>PMID: 23284789</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive immunity ; Adaptive systems ; Antigen presentation ; Antigen-presenting cells ; Antigen-Presenting Cells - immunology ; Apoptosis ; Biology ; Breast cancer ; Cancer ; Cancer immunotherapy ; CD56 antigen ; CD56 Antigen - immunology ; CD95 antigen ; Cell culture ; Cell death ; Cell Differentiation ; Cytokines ; Cytotoxicity ; Cytotoxicity, Immunologic - immunology ; Data processing ; Dendritic cells ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; Fas antigen ; FasL protein ; Flow Cytometry ; Genotype & phenotype ; Granzyme B ; Granzymes - immunology ; Granzymes - metabolism ; Health sciences ; Hematology ; Hospitals ; Humans ; Immune response ; Immune system ; Immunogenicity ; Immunology ; Immunostimulation ; Immunotherapy ; Infectious diseases ; Interleukin 15 ; Interleukin-15 - immunology ; Killer Cells, Natural - immunology ; Laboratories ; Life sciences ; Ligands ; Lymphocytes ; Lymphocytes T ; Medicine ; Monocytes ; Monocytes - cytology ; Monocytes - immunology ; Myeloid Cells - immunology ; Natural killer cells ; Neoplasms - immunology ; Neoplasms - metabolism ; Neoplasms - pathology ; Perforin ; Toxicity ; TRAIL protein ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51851</ispartof><rights>2012 Anguille et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Concerning their cytotoxic activity, we demonstrate that IL-15 DCs are able to induce apoptotic cell death of the human K562 tumor cell line, while sparing tumor antigen-specific T cells. The cytotoxicity of IL-15 DCs is predominantly mediated by granzyme B and, to a small extent, by tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, Fas ligand and TNF-α. In conclusion, our data provide evidence of a previously unappreciated role for IL-15 in the differentiation of human monocytes towards killer DCs. 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Much current research in the field of DC-based immunotherapy focuses on optimizing the culture conditions for in vitro DC generation in order to assure that DCs with the best possible immunogenic qualities are being used for immunotherapy. In this context, monocyte-derived DCs that are alternatively induced by interleukin-15 (IL-15 DCs) have attracted recent attention due to their superior immunostimulatory characteristics. In this study, we show that IL-15 DCs, in addition to potent tumor antigen-presenting function, possess tumoricidal potential and thus qualify for the designation of killer DCs. Notwithstanding marked expression of the natural killer (NK) cell marker CD56 on a subset of IL-15 DCs, we found no evidence of a further phenotypic overlap between IL-15 DCs and NK cells. Allostimulation and antigen presentation assays confirmed that IL-15 DCs should be regarded as bona fide myeloid DCs not only from the phenotypic but also from the functional point of view. Concerning their cytotoxic activity, we demonstrate that IL-15 DCs are able to induce apoptotic cell death of the human K562 tumor cell line, while sparing tumor antigen-specific T cells. The cytotoxicity of IL-15 DCs is predominantly mediated by granzyme B and, to a small extent, by tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, Fas ligand and TNF-α. In conclusion, our data provide evidence of a previously unappreciated role for IL-15 in the differentiation of human monocytes towards killer DCs. The observation that IL-15 DCs have killer DC capacity lends further support to their implementation in DC-based immunotherapy protocols.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23284789</pmid><doi>10.1371/journal.pone.0051851</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1327218318 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adaptive immunity Adaptive systems Antigen presentation Antigen-presenting cells Antigen-Presenting Cells - immunology Apoptosis Biology Breast cancer Cancer Cancer immunotherapy CD56 antigen CD56 Antigen - immunology CD95 antigen Cell culture Cell death Cell Differentiation Cytokines Cytotoxicity Cytotoxicity, Immunologic - immunology Data processing Dendritic cells Dendritic Cells - cytology Dendritic Cells - immunology Fas antigen FasL protein Flow Cytometry Genotype & phenotype Granzyme B Granzymes - immunology Granzymes - metabolism Health sciences Hematology Hospitals Humans Immune response Immune system Immunogenicity Immunology Immunostimulation Immunotherapy Infectious diseases Interleukin 15 Interleukin-15 - immunology Killer Cells, Natural - immunology Laboratories Life sciences Ligands Lymphocytes Lymphocytes T Medicine Monocytes Monocytes - cytology Monocytes - immunology Myeloid Cells - immunology Natural killer cells Neoplasms - immunology Neoplasms - metabolism Neoplasms - pathology Perforin Toxicity TRAIL protein Tumor necrosis factor-TNF Tumor necrosis factor-α |
| title | Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T08%3A05%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-15-induced%20CD56(+)%20myeloid%20dendritic%20cells%20combine%20potent%20tumor%20antigen%20presentation%20with%20direct%20tumoricidal%20potential&rft.jtitle=PloS%20one&rft.au=Anguille,%20S%C3%A9bastien&rft.date=2012-12-28&rft.volume=7&rft.issue=12&rft.spage=e51851&rft.pages=e51851-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051851&rft_dat=%3Cproquest_plos_%3E2945534771%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1327218318&rft_id=info:pmid/23284789&rft_doaj_id=oai_doaj_org_article_bdc251ecc6b34a2f84ab43a8508b427d&rfr_iscdi=true |