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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma
Authors: Tirapu, I. (Íñigo)
Huarte, E. (Eduardo)
Guiducci, C. (Cristiana)
Arina, A. (Ainhoa)
Zaratiegui, M. (Mikel)
Murillo, O. (Oihana)
Gonzalez, A. (Álvaro)
Berasain, C. (Carmen)
Berraondo, P. (Pedro)
Fortes, P. (Puri)
Prieto, J. (Jesús)
Colombo, M.P. (Mario P.)
Chen, L. (Lieping)
Melero, I. (Ignacio)
Keywords: Adenocarcinoma/immunology
Antigens, CD80/immunology
Colonic Neoplasms/immunology
Issue Date: 2006
Publisher: American Association for Cancer Research
Publisher version: http://cancerres.aacrjournals.org/content/66/4/2442
ISSN: 1538-7445
Citation: Tirapu I, Huarte E, Guiducci C, Arina A, Zaratiegui M, Murillo O, et al. Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma. Cancer Res 2006 Feb 15;66(4):2442-2450.
Abstract
Artificially enforced expression of CD80 (B7-1) and CD86 (B7-2) on tumor cells renders them more immunogenic by triggering the CD28 receptor on T cells. The enigma is that such B7s interact with much higher affinity with CTLA-4 (CD152), an inhibitory receptor expressed by activated T cells. We show that unmutated CD80 is spontaneously expressed at low levels by mouse colon carcinoma cell lines and other transplantable tumor cell lines of various tissue origins. Silencing of CD80 by interfering RNA led to loss of tumorigenicity of CT26 colon carcinoma in immunocompetent mice, but not in immunodeficient Rag-/- mice. CT26 tumor cells bind CTLA-4Ig, but much more faintly with a similar CD28Ig chimeric protein, thus providing an explanation for the dominant inhibitory effects on tumor immunity displayed by CD80 at that expression level. Interestingly, CD80-negative tumor cell lines such as MC38 colon carcinoma and B16 melanoma express CD80 at dim levels during in vivo growth in syngeneic mice. Therefore, low CD80 surface expression seems to give an advantage to cancer cells against the immune system. Our findings are similar with the inhibitory role described for the dim CD80 expression on immature dendritic cells, providing an explanation for the low levels of CD80 expression described in various human malignancies.
Permanent link: http://hdl.handle.net/10171/21800
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Vectores - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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