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dc.creatorLevy, Estrella Mariel-
dc.creatorSycz, Gabriela-
dc.creatorArriaga, Juan Martín-
dc.creatorBarrio, Maria Marcela-
dc.creatorVon Euw, Erika María-
dc.creatorMorales, Sergio Bayo-
dc.creatorGonzález, Mariana-
dc.creatorMordoh, Jose-
dc.creatorBianchini, Michele-
dc.date2017-10-04T20:01:36Z-
dc.date2017-10-04T20:01:36Z-
dc.date2009-04-
dc.date2017-09-27T17:17:29Z-
dc.date.accessioned2019-04-29T15:35:02Z-
dc.date.available2019-04-29T15:35:02Z-
dc.date.issued2017-10-04T20:01:36Z-
dc.date.issued2017-10-04T20:01:36Z-
dc.date.issued2009-04-
dc.date.issued2017-09-27T17:17:29Z-
dc.identifierLevy, 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.identifier1753-4259-
dc.identifierhttp://hdl.handle.net/11336/25932-
dc.identifier1753-4267-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/297156-
dc.descriptionCetuximab, 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.descriptionFil: Levy, Estrella Mariel. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Sycz, Gabriela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Arriaga, Juan Martín. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Barrio, Maria Marcela. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Von Euw, Erika María. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Morales, Sergio Bayo. Hospital Municipal Dr Bernardo Houssay; Argentina-
dc.descriptionFil: González, Mariana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina-
dc.descriptionFil: 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.descriptionFil: Bianchini, Michele. Fundación Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
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dc.languageeng-
dc.publisherSage Publications Ltd-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/abs/10.1177/1753425908101404-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1177/1753425908101404-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectCETUXIMAB-
dc.subjectCOLORECTAL CANCER-
dc.subjectANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY-
dc.subjectHLA-E-
dc.subjectBioquímica y Biología Molecular-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleCetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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