Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis

Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Korthals, Mark [verfasserIn] Safaian, Nancy Kronenwett, Ralf Maihöfer, Dagmar Schott, Matthias Papewalis, Claudia Diaz Blanco, Elena Winter, Meike Czibere, Akos Haas, Rainer Kobbe, Guido Fenk, Roland

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2007

Schlagwörter:	Dendritic Cell K562 Cell Immature Dendritic Cell Mature Dendritic Cell Mixed Leukocyte Reaction

Anmerkung:	© Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 5(2007), 1 vom: 25. Sept.
Übergeordnetes Werk:	volume:5 ; year:2007 ; number:1 ; day:25 ; month:09

Links:	Volltext

DOI / URN:	10.1186/1479-5876-5-46

Katalog-ID:	SPR028933168

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520			\|a Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia.
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allfields	10.1186/1479-5876-5-46 doi (DE-627)SPR028933168 (SPR)1479-5876-5-46-e DE-627 ger DE-627 rakwb eng Korthals, Mark verfasserin aut Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213 Safaian, Nancy aut Kronenwett, Ralf aut Maihöfer, Dagmar aut Schott, Matthias aut Papewalis, Claudia aut Diaz Blanco, Elena aut Winter, Meike aut Czibere, Akos aut Haas, Rainer aut Kobbe, Guido aut Fenk, Roland aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 5(2007), 1 vom: 25. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:5 year:2007 number:1 day:25 month:09 https://dx.doi.org/10.1186/1479-5876-5-46 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2007 1 25 09
spelling	10.1186/1479-5876-5-46 doi (DE-627)SPR028933168 (SPR)1479-5876-5-46-e DE-627 ger DE-627 rakwb eng Korthals, Mark verfasserin aut Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213 Safaian, Nancy aut Kronenwett, Ralf aut Maihöfer, Dagmar aut Schott, Matthias aut Papewalis, Claudia aut Diaz Blanco, Elena aut Winter, Meike aut Czibere, Akos aut Haas, Rainer aut Kobbe, Guido aut Fenk, Roland aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 5(2007), 1 vom: 25. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:5 year:2007 number:1 day:25 month:09 https://dx.doi.org/10.1186/1479-5876-5-46 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2007 1 25 09
allfields_unstemmed	10.1186/1479-5876-5-46 doi (DE-627)SPR028933168 (SPR)1479-5876-5-46-e DE-627 ger DE-627 rakwb eng Korthals, Mark verfasserin aut Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213 Safaian, Nancy aut Kronenwett, Ralf aut Maihöfer, Dagmar aut Schott, Matthias aut Papewalis, Claudia aut Diaz Blanco, Elena aut Winter, Meike aut Czibere, Akos aut Haas, Rainer aut Kobbe, Guido aut Fenk, Roland aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 5(2007), 1 vom: 25. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:5 year:2007 number:1 day:25 month:09 https://dx.doi.org/10.1186/1479-5876-5-46 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2007 1 25 09
allfieldsGer	10.1186/1479-5876-5-46 doi (DE-627)SPR028933168 (SPR)1479-5876-5-46-e DE-627 ger DE-627 rakwb eng Korthals, Mark verfasserin aut Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213 Safaian, Nancy aut Kronenwett, Ralf aut Maihöfer, Dagmar aut Schott, Matthias aut Papewalis, Claudia aut Diaz Blanco, Elena aut Winter, Meike aut Czibere, Akos aut Haas, Rainer aut Kobbe, Guido aut Fenk, Roland aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 5(2007), 1 vom: 25. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:5 year:2007 number:1 day:25 month:09 https://dx.doi.org/10.1186/1479-5876-5-46 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2007 1 25 09
allfieldsSound	10.1186/1479-5876-5-46 doi (DE-627)SPR028933168 (SPR)1479-5876-5-46-e DE-627 ger DE-627 rakwb eng Korthals, Mark verfasserin aut Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213 Safaian, Nancy aut Kronenwett, Ralf aut Maihöfer, Dagmar aut Schott, Matthias aut Papewalis, Claudia aut Diaz Blanco, Elena aut Winter, Meike aut Czibere, Akos aut Haas, Rainer aut Kobbe, Guido aut Fenk, Roland aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 5(2007), 1 vom: 25. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:5 year:2007 number:1 day:25 month:09 https://dx.doi.org/10.1186/1479-5876-5-46 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2007 1 25 09
language	English
source	Enthalten in Journal of translational medicine 5(2007), 1 vom: 25. Sept. volume:5 year:2007 number:1 day:25 month:09
sourceStr	Enthalten in Journal of translational medicine 5(2007), 1 vom: 25. Sept. volume:5 year:2007 number:1 day:25 month:09
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Dendritic Cell K562 Cell Immature Dendritic Cell Mature Dendritic Cell Mixed Leukocyte Reaction
isfreeaccess_bool	true
container_title	Journal of translational medicine
authorswithroles_txt_mv	Korthals, Mark @@aut@@ Safaian, Nancy @@aut@@ Kronenwett, Ralf @@aut@@ Maihöfer, Dagmar @@aut@@ Schott, Matthias @@aut@@ Papewalis, Claudia @@aut@@ Diaz Blanco, Elena @@aut@@ Winter, Meike @@aut@@ Czibere, Akos @@aut@@ Haas, Rainer @@aut@@ Kobbe, Guido @@aut@@ Fenk, Roland @@aut@@
publishDateDaySort_date	2007-09-25T00:00:00Z
hierarchy_top_id	369084136
id	SPR028933168
language_de	englisch
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. 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author	Korthals, Mark
spellingShingle	Korthals, Mark misc Dendritic Cell misc K562 Cell misc Immature Dendritic Cell misc Mature Dendritic Cell misc Mixed Leukocyte Reaction Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
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topic_title	Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis Dendritic Cell (dpeaa)DE-He213 K562 Cell (dpeaa)DE-He213 Immature Dendritic Cell (dpeaa)DE-He213 Mature Dendritic Cell (dpeaa)DE-He213 Mixed Leukocyte Reaction (dpeaa)DE-He213
topic	misc Dendritic Cell misc K562 Cell misc Immature Dendritic Cell misc Mature Dendritic Cell misc Mixed Leukocyte Reaction
topic_unstemmed	misc Dendritic Cell misc K562 Cell misc Immature Dendritic Cell misc Mature Dendritic Cell misc Mixed Leukocyte Reaction
topic_browse	misc Dendritic Cell misc K562 Cell misc Immature Dendritic Cell misc Mature Dendritic Cell misc Mixed Leukocyte Reaction
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title	Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
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title_full	Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
author_sort	Korthals, Mark
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author_browse	Korthals, Mark Safaian, Nancy Kronenwett, Ralf Maihöfer, Dagmar Schott, Matthias Papewalis, Claudia Diaz Blanco, Elena Winter, Meike Czibere, Akos Haas, Rainer Kobbe, Guido Fenk, Roland
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title_sort	monocyte derived dendritic cells generated by ifn-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
title_auth	Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
abstract	Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC). Methods To characterise the molecular differences of both DC preparations, gene expression profiling was performed using Affymetrix microarrays. The data were conformed on a protein level by immunophenotyping, and functional tests for T cell stimulation, migration and cytolytic activity were performed. Results Both methods resulted in CD11c+ CD86+ HLA-DR+ cells with a typical DC morphology that could efficiently stimulate T cells. But gene expression profiling revealed two distinct DC populations. Whereas IL-4/TNF-DC showed a higher expression of genes envolved in phagocytosis IFN-DC had higher RNA levels for markers of DC maturity and migration to the lymph nodes like DCLAMP, CCR7 and CD49d. This different orientation of both DC populations was confined by a 2.3 fold greater migration in transwell experiments (p = 0.01). Most interestingly, IFN-DC also showed higher RNA levels for markers of NK cells such as TRAIL, granzymes, KLRs and other NK cell receptors. On a protein level, intracytoplasmatic TRAIL and granzyme B were observed in 90% of IFN-DC. This translated into a cytolytic activity against K562 cells with a median specific lysis of 26% at high effector cell numbers as determined by propidium iodide uptake, whereas IL-4/TNF-DC did not induce any tumor cell lysis (p = 0.006). Thus, IFN-DC combined characteristics of mature DC and natural killer cells. Conclusion Our results suggest that IFN-DC not only stimulate adaptive but also mediate innate antitumor immune responses. Therefore, IFN-DC should be evaluated in clinical vaccination trials. In particular, this could be relevant for patients with diseases responsive to a treatment with IFN-α such as Non-Hodgkin lymphoma or chronic myeloid leukemia. © Korthals et al; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis
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author2	Safaian, Nancy Kronenwett, Ralf Maihöfer, Dagmar Schott, Matthias Papewalis, Claudia Diaz Blanco, Elena Winter, Meike Czibere, Akos Haas, Rainer Kobbe, Guido Fenk, Roland
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Monocyte derived dendritic cells generated by IFN-α acquire mature dendritic and natural killer cell properties as shown by gene expression analysis

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