کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151602 | 1090006 | 2012 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Plasmacytoid Dendritic Cells in the Tumor Microenvironment: Immune Targets for Glioma Therapeutics
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کلمات کلیدی
PDCDLNAPCGBMTLRIFN-αFlt3Lantigen-presenting cell - آنتیژن ارائه سلولinterferon α - اینترفرون αAdenoviral vector - بردار adenoviralthymidine kinase - تیمیدین کینازToll-like receptor - تیالآرPlasmacytoid dendritic cell - سلول دندریتیک پلاسماییکوئیدFMS-like tyrosine kinase 3 - مانند تریروزین کیناز 3 FMS مانندmajor histocompatibility complex - مجموعه سازگاری بافتی اصلیMHC - مجموعه سازگاری بافتی اصلیDraining lymph node - گره لنفاوی تخلیهGlioblastoma multiforme - گلیوبلاستوم مولتیفرم، گلیوبلاستوما
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Plasmacytoid Dendritic Cells in the Tumor Microenvironment: Immune Targets for Glioma Therapeutics Plasmacytoid Dendritic Cells in the Tumor Microenvironment: Immune Targets for Glioma Therapeutics](/preview/png/2151602.png)
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 8, August 2012, Pages 757-770, IN22-IN26
Journal: Neoplasia - Volume 14, Issue 8, August 2012, Pages 757-770, IN22-IN26
نویسندگان
Marianela Candolfi, Gwendalyn D. King, Kader Yagiz, James F. Curtin, Yohei Mineharu, AKM Ghulam Muhammad, David Foulad, Kurt M. Kroeger, Nick Barnett, Regis Josien, Pedro R. Lowenstein, Maria G. Castro,