Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells

Autores
Levy, Estrella Mariel; Sycz, Gabriela; Arriaga, Juan Martín; Barrio, Maria Marcela; Von Euw, Erika María; Morales, Sergio Bayo; González, Mariana; Mordoh, Jose; Bianchini, Michele
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to increase the median survival of colorectal cancer patients. We previously reported that the expression of HLA-E is significantly increased in primary human colorectal cancer, perhaps contributing to tumour escape from immune surveillance. To establish if HLA-E could be a factor that renders colorectal cancer cells less susceptible to antibody-dependent cellular cytotoxicity (ADCC), in the present study we analysed Cetuximab-mediated cytotoxicity against several colorectal cancer cell lines expressing, or not, HLA-E at the cell surface. We first observed that colorectal cancer cells treated with Cetuximab were killed more efficiently by ADCC. Interestingly, treatment of target cells with recombinant human-beta2-microglobulin inhibits Cetuximab-mediated ADCC through HLA-E membrane stabilization. The specific immunosuppressive role of HLA-E was confirmed using an anti-NKG2A monoclonal antibody, that restored the ability of immune cells to kill their target. This result demonstrates that HLA-E at the cell surface can reliably suppress the ADCC effect. On the other hand, Cetuximab induced a direct growth inhibition but only at high concentrations; furthermore, the CDC effect was quite moderate, and we failed to observe a pro-apoptotic effect. Taking into account that our findings suggest that ADCC activity is the main anti-tumour effect observed at clinically achievable concentrations of Cetuximab at the tumour site, we suggest that determination of HLA-E in colorectal cancer could be relevant to predict success of Cetuximab treatment.
Fil: Levy, Estrella Mariel. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sycz, Gabriela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arriaga, Juan Martín. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrio, Maria Marcela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Von Euw, Erika María. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Sergio Bayo. Hospital Municipal Dr Bernardo Houssay; Argentina
Fil: González, Mariana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina
Fil: Bianchini, Michele. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Cetuximab
Colorectal Cancer
Antibody-Dependent Cellular Cytotoxicity
Hla-E
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25932
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25932
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cellsLevy, Estrella MarielSycz, GabrielaArriaga, Juan MartínBarrio, Maria MarcelaVon Euw, Erika MaríaMorales, Sergio BayoGonzález, MarianaMordoh, JoseBianchini, MicheleCetuximabColorectal CancerAntibody-Dependent Cellular CytotoxicityHla-Ehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to increase the median survival of colorectal cancer patients. We previously reported that the expression of HLA-E is significantly increased in primary human colorectal cancer, perhaps contributing to tumour escape from immune surveillance. To establish if HLA-E could be a factor that renders colorectal cancer cells less susceptible to antibody-dependent cellular cytotoxicity (ADCC), in the present study we analysed Cetuximab-mediated cytotoxicity against several colorectal cancer cell lines expressing, or not, HLA-E at the cell surface. We first observed that colorectal cancer cells treated with Cetuximab were killed more efficiently by ADCC. Interestingly, treatment of target cells with recombinant human-beta2-microglobulin inhibits Cetuximab-mediated ADCC through HLA-E membrane stabilization. The specific immunosuppressive role of HLA-E was confirmed using an anti-NKG2A monoclonal antibody, that restored the ability of immune cells to kill their target. This result demonstrates that HLA-E at the cell surface can reliably suppress the ADCC effect. On the other hand, Cetuximab induced a direct growth inhibition but only at high concentrations; furthermore, the CDC effect was quite moderate, and we failed to observe a pro-apoptotic effect. Taking into account that our findings suggest that ADCC activity is the main anti-tumour effect observed at clinically achievable concentrations of Cetuximab at the tumour site, we suggest that determination of HLA-E in colorectal cancer could be relevant to predict success of Cetuximab treatment.Fil: Levy, Estrella Mariel. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sycz, Gabriela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arriaga, Juan Martín. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrio, Maria Marcela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Von Euw, Erika María. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morales, Sergio Bayo. Hospital Municipal Dr Bernardo Houssay; ArgentinaFil: González, Mariana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Cancer. Centro de Investigaciones Oncologicas; ArgentinaFil: Bianchini, Michele. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaSage Publications Ltd2009-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25932Levy, Estrella Mariel; Sycz, Gabriela; Arriaga, Juan Martín; Barrio, Maria Marcela; Von Euw, Erika María; et al.; Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells; Sage Publications Ltd; Innate Immunity; 15; 2; 4-2009; 91-1001753-42591753-4267CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/abs/10.1177/1753425908101404info:eu-repo/semantics/altIdentifier/doi/10.1177/1753425908101404info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:31Zoai:ri.conicet.gov.ar:11336/25932instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:31.778CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
title Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
spellingShingle Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
Levy, Estrella Mariel
Cetuximab
Colorectal Cancer
Antibody-Dependent Cellular Cytotoxicity
Hla-E
title_short Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
title_full Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
title_fullStr Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
title_full_unstemmed Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
title_sort Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
dc.creator.none.fl_str_mv Levy, Estrella Mariel
Sycz, Gabriela
Arriaga, Juan Martín
Barrio, Maria Marcela
Von Euw, Erika María
Morales, Sergio Bayo
González, Mariana
Mordoh, Jose
Bianchini, Michele
author Levy, Estrella Mariel
author_facet Levy, Estrella Mariel
Sycz, Gabriela
Arriaga, Juan Martín
Barrio, Maria Marcela
Von Euw, Erika María
Morales, Sergio Bayo
González, Mariana
Mordoh, Jose
Bianchini, Michele
author_role author
author2 Sycz, Gabriela
Arriaga, Juan Martín
Barrio, Maria Marcela
Von Euw, Erika María
Morales, Sergio Bayo
González, Mariana
Mordoh, Jose
Bianchini, Michele
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cetuximab
Colorectal Cancer
Antibody-Dependent Cellular Cytotoxicity
Hla-E
topic Cetuximab
Colorectal Cancer
Antibody-Dependent Cellular Cytotoxicity
Hla-E
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to increase the median survival of colorectal cancer patients. We previously reported that the expression of HLA-E is significantly increased in primary human colorectal cancer, perhaps contributing to tumour escape from immune surveillance. To establish if HLA-E could be a factor that renders colorectal cancer cells less susceptible to antibody-dependent cellular cytotoxicity (ADCC), in the present study we analysed Cetuximab-mediated cytotoxicity against several colorectal cancer cell lines expressing, or not, HLA-E at the cell surface. We first observed that colorectal cancer cells treated with Cetuximab were killed more efficiently by ADCC. Interestingly, treatment of target cells with recombinant human-beta2-microglobulin inhibits Cetuximab-mediated ADCC through HLA-E membrane stabilization. The specific immunosuppressive role of HLA-E was confirmed using an anti-NKG2A monoclonal antibody, that restored the ability of immune cells to kill their target. This result demonstrates that HLA-E at the cell surface can reliably suppress the ADCC effect. On the other hand, Cetuximab induced a direct growth inhibition but only at high concentrations; furthermore, the CDC effect was quite moderate, and we failed to observe a pro-apoptotic effect. Taking into account that our findings suggest that ADCC activity is the main anti-tumour effect observed at clinically achievable concentrations of Cetuximab at the tumour site, we suggest that determination of HLA-E in colorectal cancer could be relevant to predict success of Cetuximab treatment.
Fil: Levy, Estrella Mariel. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sycz, Gabriela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arriaga, Juan Martín. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrio, Maria Marcela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Von Euw, Erika María. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Sergio Bayo. Hospital Municipal Dr Bernardo Houssay; Argentina
Fil: González, Mariana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina
Fil: Bianchini, Michele. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to increase the median survival of colorectal cancer patients. We previously reported that the expression of HLA-E is significantly increased in primary human colorectal cancer, perhaps contributing to tumour escape from immune surveillance. To establish if HLA-E could be a factor that renders colorectal cancer cells less susceptible to antibody-dependent cellular cytotoxicity (ADCC), in the present study we analysed Cetuximab-mediated cytotoxicity against several colorectal cancer cell lines expressing, or not, HLA-E at the cell surface. We first observed that colorectal cancer cells treated with Cetuximab were killed more efficiently by ADCC. Interestingly, treatment of target cells with recombinant human-beta2-microglobulin inhibits Cetuximab-mediated ADCC through HLA-E membrane stabilization. The specific immunosuppressive role of HLA-E was confirmed using an anti-NKG2A monoclonal antibody, that restored the ability of immune cells to kill their target. This result demonstrates that HLA-E at the cell surface can reliably suppress the ADCC effect. On the other hand, Cetuximab induced a direct growth inhibition but only at high concentrations; furthermore, the CDC effect was quite moderate, and we failed to observe a pro-apoptotic effect. Taking into account that our findings suggest that ADCC activity is the main anti-tumour effect observed at clinically achievable concentrations of Cetuximab at the tumour site, we suggest that determination of HLA-E in colorectal cancer could be relevant to predict success of Cetuximab treatment.
publishDate 2009
dc.date.none.fl_str_mv 2009-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25932
Levy, Estrella Mariel; Sycz, Gabriela; Arriaga, Juan Martín; Barrio, Maria Marcela; Von Euw, Erika María; et al.; Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells; Sage Publications Ltd; Innate Immunity; 15; 2; 4-2009; 91-100
1753-4259
1753-4267
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25932
identifier_str_mv Levy, Estrella Mariel; Sycz, Gabriela; Arriaga, Juan Martín; Barrio, Maria Marcela; Von Euw, Erika María; et al.; Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells; Sage Publications Ltd; Innate Immunity; 15; 2; 4-2009; 91-100
1753-4259
1753-4267
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1177/1753425908101404
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Sage Publications Ltd
publisher.none.fl_str_mv Sage Publications Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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