CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy

Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for acti...
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Autor*in:	Stine Sofie Frank Lende [verfasserIn] Marie Høst Pahus [verfasserIn] Ida Monrad [verfasserIn] Rikke Olesen [verfasserIn] Anna R. Mahr [verfasserIn] Line K. Vibholm [verfasserIn] Lars Østergaard [verfasserIn] Ole Schmeltz Søgaard [verfasserIn] Anna Halling Folkmar Andersen [verfasserIn] Paul W. Denton [verfasserIn] Martin Tolstrup [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1

Übergeordnetes Werk:	In: Frontiers in Cellular and Infection Microbiology - Frontiers Media S.A., 2016, 12(2022)
Übergeordnetes Werk:	volume:12 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcimb.2022.919097

Katalog-ID:	DOAJ027031144

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spelling	10.3389/fcimb.2022.919097 doi (DE-627)DOAJ027031144 (DE-599)DOAJ97ac420052f243f2b252a4c2ec4834b0 DE-627 ger DE-627 rakwb eng QR1-502 Stine Sofie Frank Lende verfasserin aut CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1 Microbiology Marie Høst Pahus verfasserin aut Ida Monrad verfasserin aut Rikke Olesen verfasserin aut Rikke Olesen verfasserin aut Anna R. Mahr verfasserin aut Line K. Vibholm verfasserin aut Line K. Vibholm verfasserin aut Lars Østergaard verfasserin aut Lars Østergaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Anna Halling Folkmar Andersen verfasserin aut Paul W. Denton verfasserin aut Martin Tolstrup verfasserin aut Martin Tolstrup verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 12(2022) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:12 year:2022 https://doi.org/10.3389/fcimb.2022.919097 kostenfrei https://doaj.org/article/97ac420052f243f2b252a4c2ec4834b0 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2022.919097/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_2014 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 12 2022
allfields_unstemmed	10.3389/fcimb.2022.919097 doi (DE-627)DOAJ027031144 (DE-599)DOAJ97ac420052f243f2b252a4c2ec4834b0 DE-627 ger DE-627 rakwb eng QR1-502 Stine Sofie Frank Lende verfasserin aut CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1 Microbiology Marie Høst Pahus verfasserin aut Ida Monrad verfasserin aut Rikke Olesen verfasserin aut Rikke Olesen verfasserin aut Anna R. Mahr verfasserin aut Line K. Vibholm verfasserin aut Line K. Vibholm verfasserin aut Lars Østergaard verfasserin aut Lars Østergaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Anna Halling Folkmar Andersen verfasserin aut Paul W. Denton verfasserin aut Martin Tolstrup verfasserin aut Martin Tolstrup verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 12(2022) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:12 year:2022 https://doi.org/10.3389/fcimb.2022.919097 kostenfrei https://doaj.org/article/97ac420052f243f2b252a4c2ec4834b0 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2022.919097/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_2014 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 12 2022
allfieldsGer	10.3389/fcimb.2022.919097 doi (DE-627)DOAJ027031144 (DE-599)DOAJ97ac420052f243f2b252a4c2ec4834b0 DE-627 ger DE-627 rakwb eng QR1-502 Stine Sofie Frank Lende verfasserin aut CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1 Microbiology Marie Høst Pahus verfasserin aut Ida Monrad verfasserin aut Rikke Olesen verfasserin aut Rikke Olesen verfasserin aut Anna R. Mahr verfasserin aut Line K. Vibholm verfasserin aut Line K. Vibholm verfasserin aut Lars Østergaard verfasserin aut Lars Østergaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Anna Halling Folkmar Andersen verfasserin aut Paul W. Denton verfasserin aut Martin Tolstrup verfasserin aut Martin Tolstrup verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 12(2022) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:12 year:2022 https://doi.org/10.3389/fcimb.2022.919097 kostenfrei https://doaj.org/article/97ac420052f243f2b252a4c2ec4834b0 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2022.919097/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_2014 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 12 2022
allfieldsSound	10.3389/fcimb.2022.919097 doi (DE-627)DOAJ027031144 (DE-599)DOAJ97ac420052f243f2b252a4c2ec4834b0 DE-627 ger DE-627 rakwb eng QR1-502 Stine Sofie Frank Lende verfasserin aut CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1 Microbiology Marie Høst Pahus verfasserin aut Ida Monrad verfasserin aut Rikke Olesen verfasserin aut Rikke Olesen verfasserin aut Anna R. Mahr verfasserin aut Line K. Vibholm verfasserin aut Line K. Vibholm verfasserin aut Lars Østergaard verfasserin aut Lars Østergaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Ole Schmeltz Søgaard verfasserin aut Anna Halling Folkmar Andersen verfasserin aut Paul W. Denton verfasserin aut Martin Tolstrup verfasserin aut Martin Tolstrup verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 12(2022) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:12 year:2022 https://doi.org/10.3389/fcimb.2022.919097 kostenfrei https://doaj.org/article/97ac420052f243f2b252a4c2ec4834b0 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2022.919097/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_2014 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 12 2022
language	English
source	In Frontiers in Cellular and Infection Microbiology 12(2022) volume:12 year:2022
sourceStr	In Frontiers in Cellular and Infection Microbiology 12(2022) volume:12 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1 Microbiology
isfreeaccess_bool	true
container_title	Frontiers in Cellular and Infection Microbiology
authorswithroles_txt_mv	Stine Sofie Frank Lende @@aut@@ Marie Høst Pahus @@aut@@ Ida Monrad @@aut@@ Rikke Olesen @@aut@@ Anna R. Mahr @@aut@@ Line K. Vibholm @@aut@@ Lars Østergaard @@aut@@ Ole Schmeltz Søgaard @@aut@@ Anna Halling Folkmar Andersen @@aut@@ Paul W. Denton @@aut@@ Martin Tolstrup @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	664968554
id	DOAJ027031144
language_de	englisch
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callnumber-first	Q - Science
author	Stine Sofie Frank Lende
spellingShingle	Stine Sofie Frank Lende misc QR1-502 misc biomarker misc CD169 misc toll-like receptor 9 (TLR9) misc immunotherapy misc HIV-1 misc Microbiology CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy
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topic_title	QR1-502 CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy biomarker CD169 toll-like receptor 9 (TLR9) immunotherapy HIV-1
topic	misc QR1-502 misc biomarker misc CD169 misc toll-like receptor 9 (TLR9) misc immunotherapy misc HIV-1 misc Microbiology
topic_unstemmed	misc QR1-502 misc biomarker misc CD169 misc toll-like receptor 9 (TLR9) misc immunotherapy misc HIV-1 misc Microbiology
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title	CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy
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title_full	CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy
author_sort	Stine Sofie Frank Lende
journal	Frontiers in Cellular and Infection Microbiology
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author_browse	Stine Sofie Frank Lende Marie Høst Pahus Ida Monrad Rikke Olesen Anna R. Mahr Line K. Vibholm Lars Østergaard Ole Schmeltz Søgaard Anna Halling Folkmar Andersen Paul W. Denton Martin Tolstrup
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title_sort	cd169 (siglec-1) as a robust human cell biomarker of toll-like receptor 9 agonist immunotherapy
callnumber	QR1-502
title_auth	CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy
abstract	Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.
abstractGer	Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.
abstract_unstemmed	Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p<0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.
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title_short	CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy
url	https://doi.org/10.3389/fcimb.2022.919097 https://doaj.org/article/97ac420052f243f2b252a4c2ec4834b0 https://www.frontiersin.org/articles/10.3389/fcimb.2022.919097/full https://doaj.org/toc/2235-2988
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author2	Marie Høst Pahus Ida Monrad Rikke Olesen Anna R. Mahr Line K. Vibholm Lars Østergaard Ole Schmeltz Søgaard Anna Halling Folkmar Andersen Paul W. Denton Martin Tolstrup
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