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dc.contributor.author
Candolfi, Marianela
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dc.contributor.author
King, Gwendalyn D.
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Yagiz, Kader
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Curtin, James F.
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Mineharu, Yohei
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Ghulam Muhammad, A.K.M.
dc.contributor.author
Foulad, David
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Kroeger, Kurt M.
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Barnett, Nick
dc.contributor.author
Josien, Regis
dc.contributor.author
Lowenstein, Pedro R.
dc.contributor.author
Castro, Maria Gabriela
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dc.date.available
2019-01-04T13:23:50Z
dc.date.issued
2012-08
dc.identifier.citation
Candolfi, Marianela; King, Gwendalyn D.; Yagiz, Kader; Curtin, James F.; Mineharu, Yohei; et al.; Plasmacytoid Dendritic Cells In The Tumor Microenvironment: Immune Targets For Glioma Therapeutics; Neoplasia Press; Neoplasia; 14; 8; 8-2012; 757-770
dc.identifier.issn
1522-8002
dc.identifier.uri
http://hdl.handle.net/11336/67377
dc.description.abstract
Adenovirus-mediated delivery of the immune-stimulatory cytokine Flt3L and the conditionally cytotoxic thymidine kinase (TK) induces tumor regression and long-term survival in preclinical glioma (glioblastoma multiforme [GBM]) models. Flt3L induces expansion and recruitment of plasmacytoid dendritic cells (pDCs) into the brain. Although pDCs can present antigen and produce powerful inflammatory cytokines, that is, interferon α (IFN-α), their role in tumor immunology remains debated. Thus, we studied the role of pDCs and IFN-α in Ad.TK/GCV + Ad.Flt3L-mediated anti-GBM therapeutic efficacy. Our data indicate that the combined gene therapy induced recruitment of plasmacytoid DCs (pDCs) into the tumor mass; which were capable of in vivo phagocytosis, IFN-α release, and T-cell priming. Thus, we next used either pDCs or an Ad vector encoding IFN-α delivered within the tumor microenvironment. When rats were treated with Ad.TK/GCV in combination with pDCs or Ad-IFN-α, they exhibited 35% and 50% survival, respectively. However, whereas intracranial administration of Ad.TK/GCV + Ad.Flt3L exhibited a high safety profile, Ad-IFN-α led to severe local inflammation, with neurologic and systemic adverse effects. To elucidate whether the efficacy of the immunotherapy was dependent on IFN-α-secreting pDCs, we administered an Ad vector encoding B18R, an IFN-α antagonist, which abrogated the antitumoral effect of Ad.TK/GCV + Ad.Flt3L. Our data suggest that IFN-α release by activated pDCs plays a critical role in the antitumor effect mediated by Ad.TK/GCV + Ad.Flt3L. In summary, taken together, our results demonstrate that pDCs mediate anti-GBM therapeutic efficacy through the production of IFN-α, thus manipulation of pDCs constitutes an attractive new therapeutic target for the treatment of GBM. © 2012 Neoplasia Press, Inc. All rights reserved.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Neoplasia Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Glioblastoma
dc.subject
Plasmacyotid Dendritic Cells
dc.subject
Gene Therapy
dc.subject
Ifn-Alpha
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Otras Biotecnologías de la Salud
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dc.subject.classification
Biotecnología de la Salud
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Plasmacytoid Dendritic Cells In The Tumor Microenvironment: Immune Targets For Glioma Therapeutics
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-02T19:38:35Z
dc.journal.volume
14
dc.journal.number
8
dc.journal.pagination
757-770
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
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Fil: King, Gwendalyn D.. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
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Fil: Yagiz, Kader. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Curtin, James F.. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Mineharu, Yohei. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Ghulam Muhammad, A.K.M.. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Foulad, David. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Kroeger, Kurt M.. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Barnett, Nick. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos
dc.description.fil
Fil: Josien, Regis. Inserm; Francia
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Fil: Lowenstein, Pedro R.. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos. University of Michigan; Estados Unidos
dc.description.fil
Fil: Castro, Maria Gabriela. Cedars Sinai Medical Center. Gene Therapeutics Research Institute; Estados Unidos. University of Michigan; Estados Unidos
dc.journal.title
Neoplasia
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1593/neo.12794
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1476558612800091
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