IFN-γ-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer
IFN-γ-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer
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DOI：
10.1016/j.vaccine.2010.03.007
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发表时间：
2010-04-30
期刊：
影响因子：
5.5
通讯作者：
Sartoris, Silvia
中科院分区：
文献类型：
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作者：
Martini, Matteo;Testi, Maria Grazia;Sartoris, Silvia
B7-1的De nova表达损害TRAMP-C2小鼠前列腺腺癌（TRAMP-C2/B7）的致瘤性，但除非在用IFN-γ体外处理之后，否则其不引起针对TRAMP-C2亲本肿瘤的保护性应答。TRAMP-C2细胞分泌TGF-β并显示低MHC-I表达。用IFN-γ治疗通过诱导一些APM组分和拮抗TGF-β的免疫抑制活性来增加MHC-I表达。因此，用TRAMP-C2/B7免疫赋予针对TRAMP-C2衍生的肿瘤的保护作用，其功能在于IFN-γ介导的APM表达或TGF-β信号传导的微调调节。为了探索可能的临床转化，我们通过分泌IFN-γ的基因工程MSC将IFN-γ递送至TRAMP-C2肿瘤部位。(C)2010爱思唯尔有限公司版权所有。
De nova expression of B7-1 impaired tumorigenicity of TRAMP-C2 mouse prostate adenocarcinoma (TRAMP-C2/B7), but it did not elicit a protective response against TRAMP-C2 parental tumor, unless after in vitro treatment with IFN-gamma. TRAMP-C2 cells secrete TGF-beta and show low MHC-I expression. Treatment with IFN-gamma increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-beta. Thus, immunization with TRAMP-C2/B7 conferred protection against TRAMP-C2-derived tumors in function of the IFN-gamma-mediated fine-tuned modulation of either APM expression or TGF-beta signaling. To explore possible clinical translation, we delivered IFN-gamma to TRAMP-C2 tumor site by means of genetically engineered MSCs secreting IFN-gamma. (C) 2010 Elsevier Ltd. All rights reserved.