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dc.contributor.author Levy, Estrella Mariel
dc.contributor.author Sycz, Gabriela
dc.contributor.author Arriaga, Juan Martín
dc.contributor.author Barrio, Maria Marcela
dc.contributor.author Von Euw, Erika María
dc.contributor.author Morales, Sergio Bayo
dc.contributor.author González, Mariana
dc.contributor.author Mordoh, Jose
dc.contributor.author Bianchini, Michele
dc.date.available 2017-10-04T20:01:36Z
dc.date.issued 2009-04
dc.identifier.citation 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
dc.identifier.issn 1753-4259
dc.identifier.uri http://hdl.handle.net/11336/25932
dc.description.abstract 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.
dc.format application/pdf
dc.language.iso eng
dc.publisher Sage Publications Ltd
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject CETUXIMAB
dc.subject COLORECTAL CANCER
dc.subject ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY
dc.subject HLA-E
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-09-27T17:17:29Z
dc.identifier.eissn 1753-4267
dc.journal.volume 15
dc.journal.number 2
dc.journal.pagination 91-100
dc.journal.pais Estados Unidos
dc.journal.ciudad Los Angeles
dc.description.fil Fil: Levy, Estrella Mariel. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Sycz, Gabriela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Arriaga, Juan Martín. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Barrio, Maria Marcela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Von Euw, Erika María. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Morales, Sergio Bayo. Hospital Municipal Dr Bernardo Houssay; Argentina
dc.description.fil Fil: González, Mariana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
dc.description.fil 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
dc.description.fil Fil: Bianchini, Michele. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title Innate Immunity
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/abs/10.1177/1753425908101404
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1177/1753425908101404


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)