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用可溶性程序性死亡受体-1(sPD-1)阻断B7-H1可增强对小鼠肝癌的免疫力。

Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma.

作者信息

He Lanxiang, Zhang Guimei, He Yufei, Zhu Hangang, Zhang Hui, Feng Zuohua

机构信息

Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

出版信息

Anticancer Res. 2005 Sep-Oct;25(5):3309-13.

Abstract

BACKGROUND

The B7-H1/PD-1 pathway has been demonstrated to be involved in tumor evasion. In a previous study, we constructed a eukaryotic expression plasmid (pPD-1A), which expresses soluble PD-1 (sPD-1). In this study, the question of whether or not the blockade of B7-H1 with sPD-1 in vivo and vitro can improve antitumor immunity was investigated.

MATERIALS AND METHODS

The proliferation of lymphocytes activated by dendritic cells (DCs), which were treated with sPD-1 in vitro, was detected with MTT colorimetry. Mice inoculated with H22 cells were treated by intramuscular injection with pPD-1A. The mRNA expression was analyzed with RT-PCR.

RESULTS

The early activation of lymphocytes in vitro was partly improved by sPD-1 blockade. The growth of H22 cells was inhibited significantly after pPD-1A administration. The mRNA expression of 4-1BB, B7.1, IFN-gamma and TNF-alpha of lymphocytes was up-regulated and that of OX40 and IL-10 was down-regulated after pPD-1A administration.

CONCLUSION

Blockade of the PD-1/B7-H1 pathway with sPD-1 may be a promising strategy for immunotherapy for hepatocarcinoma. Both cytokines and co-stimulatory molecules of lymphocytes could be regulated by sPD-1 blockade.

摘要

背景

B7-H1/PD-1通路已被证明与肿瘤逃逸有关。在之前的一项研究中,我们构建了一个表达可溶性PD-1(sPD-1)的真核表达质粒(pPD-1A)。在本研究中,我们探讨了在体内和体外使用sPD-1阻断B7-H1是否能增强抗肿瘤免疫力。

材料与方法

用MTT比色法检测体外经sPD-1处理的树突状细胞(DCs)激活的淋巴细胞的增殖情况。给接种H22细胞的小鼠肌肉注射pPD-1A进行治疗。用RT-PCR分析mRNA表达。

结果

sPD-1阻断可部分改善体外淋巴细胞的早期激活。给予pPD-1A后,H22细胞的生长受到显著抑制。给予pPD-1A后,淋巴细胞的4-1BB、B7.1、IFN-γ和TNF-α的mRNA表达上调,而OX40和IL-10的mRNA表达下调。

结论

用sPD-1阻断PD-1/B7-H1通路可能是肝癌免疫治疗的一种有前景的策略。sPD-1阻断可调节淋巴细胞的细胞因子和共刺激分子。

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