دورية أكاديمية
PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model.
| العنوان: | PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model. |
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| المؤلفون: | Shi-Dong Ma, Xuequn Xu, Richard Jones, Henri-Jacques Delecluse, Nicholas A Zumwalde, Akshat Sharma, Jenny E Gumperz, Shannon C Kenney |
| المصدر: | PLoS Pathogens, Vol 12, Iss 5, p e1005642 (2016) |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | Epstein-Barr virus (EBV) infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG) mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV-infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81) in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1005642 |
| URL الوصول: | https://doaj.org/article/32a311329ea246f39fc2ae60da42eecc |
| رقم الأكسشن: | edsdoj.32a311329ea246f39fc2ae60da42eecc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1005642 |