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dc.contributor.author
Spaapen, Robbert
dc.contributor.author
Leung, Michael Y. K.
dc.contributor.author
Fuertes, Mercedes Beatriz
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Kline, Justin P.
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Zhang, Long
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Zheng, Yan
dc.contributor.author
Fu, Yang Xin
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Luo, Xixi
dc.contributor.author
Cohen, Kenneth S.
dc.contributor.author
Gajewski, Thomas F.
dc.date.available
2016-08-30T14:08:12Z
dc.date.issued
2014-10-15
dc.identifier.citation
Spaapen, Robbert ; Leung, Michael Y. K.; Fuertes, Mercedes Beatriz; Kline, Justin P.; Zhang, Long ; et al.; Therapeutic activity of high-dose intratumoral IFN-β requires direct effect on the tumor vasculature; Amer Assoc Immunologists; Journal Of Immunology; 193; 8; 15-10-2014; 4254-4260
dc.identifier.issn
0022-1767
dc.identifier.uri
http://hdl.handle.net/11336/7346
dc.description.abstract
Endogenous type I IFN production after innate immune recognition of tumor cells is critical for generating natural adaptive immune responses against tumors in vivo. We recently have reported that targeting low doses of IFN-β to the tumor microenvironment using tumor-specific mAbs can facilitate antitumor immunity, which could be augmented further with PD-L1/PD-1 blockade. However, sustained high doses of type I IFNs in the tumor microenvironment, which are potently therapeutic alone, may function through distinct mechanisms. In the current report, we demonstrate that high-dose intratumoral type I IFNs indeed exerted a profound therapeutic effect in the murine B16 model, which unexpectedly did not increase T cell responses. Moreover, bone marrow chimeras revealed a role for type I IFN signaling on nonhematopoietic cells, and most of the therapeutic effect was retained in mice deficient in T, B, and NK cells. Rather, the tumor vasculature was ablated with high-dose intratumoral IFN-β, and conditional deletion of IFN-α/βR in Tie2-positive vascular endothelial cells eliminated most of the antitumor activity. Therefore, the major component of the antitumor activity of sustained high doses of type I IFNs occurs through a direct antiangiogenic effect. Our data help resolve conditions under which distinct antitumor mechanisms of type I IFNs are operational in vivo.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Amer Assoc Immunologists
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Interferon Beta
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Tumor
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Vasculature
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Therapy
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Experimental Melanoma
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Patología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Therapeutic activity of high-dose intratumoral IFN-β requires direct effect on the tumor vasculature
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-06-15T19:08:29Z
dc.identifier.eissn
1550-6606
dc.journal.volume
193
dc.journal.number
8
dc.journal.pagination
4254-4260
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Spaapen, Robbert . University Of Chicago; Estados Unidos
dc.description.fil
Fil: Leung, Michael Y. K.. University Of Chicago; Estados Unidos
dc.description.fil
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. University Of Chicago; Estados Unidos
dc.description.fil
Fil: Kline, Justin P.. University Of Chicago; Estados Unidos
dc.description.fil
Fil: Zhang, Long . University Of Chicago; Estados Unidos
dc.description.fil
Fil: Zheng, Yan . University Of Chicago; Estados Unidos
dc.description.fil
Fil: Fu, Yang Xin. University Of Chicago; Estados Unidos
dc.description.fil
Fil: Luo, Xixi . University Of Chicago; Estados Unidos
dc.description.fil
Fil: Cohen, Kenneth S. . University Of Chicago; Estados Unidos
dc.description.fil
Fil: Gajewski, Thomas F. . University Of Chicago; Estados Unidos
dc.journal.title
Journal Of Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.4049/jimmunol.1401109
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/193/8/4254.long
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