کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10962372 | 1102632 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enhancement of fibroblast activation protein α-based vaccines and adenovirus boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1 tumor bearing mice
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کلمات کلیدی
TregsFAPαVascular endothelial growth factor alphaT helper type 1Th1CAFsHGFECMRADqRT-PCRSDF-1Adenovirus - آدنوویروسRecombinant adenovirus - آدنویروس مجددPrime-boost strategy - استراتژی تقویت نخستینInterleukin-10 - اینترلوکین 10Immunosuppression - سرکوب سیستم ایمنیRegulatory T cells - سلولهای تی تنظیمکنندهCyclophosphamide - سیکلوفسفامید stromal cell-derived factor-1 - فاکتور 1 حاصل از استروما سلولHematopoietic growth factor - فاکتور رشد هماتوپاتیCancer-associated fibroblasts - فیبروبلاست های مرتبط با سرطانExtracellular matrix - ماتریکس خارج سلولیCancer vaccine - واکسن سرطانیquantitative real time polymerase chain reaction - واکنش زنجیره ای پلیمراز واقعی در زمان واقعیFibroblast activation protein α - پروتئین فعال سازی فیبربلاست α
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are the main type of cells in the tumor microenvironment which offer nutrition and protection to the tumor and regulate immunosuppression. To eliminate CAFs, a vaccine targeting FAPα may be used with a heterologous prime-boost strategy to enhance the FAPα-specific cellular immunity. Here, a FAP vaccine using a recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine reported in our previous work. Although the DNA prime-rAd boost strategy enhanced FAPα-specific immune responses, improvement of anti-tumor immunity effects was not observed. Examination of immunosuppressive factors revealed that high expression of the IL-10 cytokine was considered the main cause of the failure of the prime-boost strategy. However, heterologous vaccination in combination with a low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production and promote a shift from immunosuppression to immunopotentiation, resulted in enhanced effects in terms of numbers of effector T cells and tumor growth inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was inhibited markedly when the prime-boost strategy was combined with CY in both the prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing mice was also prolonged significantly. With the reduction of IL-10, enhancement of the anti-tumor effect by the prime-boost strategy was observed. These results suggest that FAPα-targeted rAd boosting in combination with CY is an attractive approach to overcoming immunosuppression in cancer vaccines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 34, Issue 38, 31 August 2016, Pages 4526-4535
Journal: Vaccine - Volume 34, Issue 38, 31 August 2016, Pages 4526-4535
نویسندگان
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Hai-Hong Zhang, Wei Kong, Xiang-Hui Yu,