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Artículo

Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function

Gatti, Gerardo AlbertoIcon ; Núñez, NicolásIcon ; Nocera, David AndresIcon ; Dejader, Lien; Libert, Claude; Giraudo, Constancio Alberto; Maccioni, MarianaIcon
Fecha de publicación: 05/2013
Editorial: Wiley VCH Verlag
Revista: European Journal of Immunology
ISSN: 0014-2980
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.
Palabras clave: Ifnbeta , Dsrna , Tlr3 , Dendritic Cells , Tumor Immunity
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info:eu-repo/semantics/openAccess 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)
Identificadores
URI: http://hdl.handle.net/11336/25788
DOI: http://dx.doi.org/10.1002/eji.201242902
URL: http://onlinelibrary.wiley.com/doi/10.1002/eji.201242902/abstract
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Gatti, Gerardo Alberto; Núñez, Nicolás; Nocera, David Andres; Dejader, Lien; Libert, Claude; et al.; Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function; Wiley VCH Verlag; European Journal of Immunology; 43; 7; 5-2013; 1849-1861
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