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程序性死亡蛋白1的表达与骨肉瘤的进展相关。

Expression of programmed death 1 is correlated with progression of osteosarcoma.

作者信息

Zheng Wenjie, Xiao Hong, Liu Huan, Zhou Yue

机构信息

Department of Orthopedics, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.

出版信息

APMIS. 2015 Feb;123(2):102-7. doi: 10.1111/apm.12311. Epub 2014 Sep 25.

Abstract

Accumulating bodies of evidence indicate that immune dysregulation plays a key role in the development of osteosarcoma (OS). Programmed death 1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T-cell inhibition upon binding with its ligand. Researches on PD-1 and OS remain extremely limited. Here, we investigated whether PD-1 could be involved in the development of OS. Expression of PD-1 was measured by flow cytometry on peripheral CD4+ and CD8+ T cells from 56 OS cases and 42 healthy controls. Data revealed that percentages of PD-1 were significantly upregulated on both peripheral CD4+ and CD8+ T cells from OS patients (p < 0.001 and p < 0.001, respectively). Patients with different tumor locations did not present obvious variations in PD-1 level. However, patients with metastasis showed significantly higher level of PD-1 on CD4+ T cells than those without metastasis (p < 0.001). Furthermore, PD-1 expression on CD4+ T cells started to increase in stage III, whereas PD-1 expression on CD8+ T cells started to increase in stage II. In addition, patients with pathological fracture were observed to have elevated PD-1 on both CD4+ and CD8+ T cells. These data suggest that PD-1 is involved in the pathogenesis of OS, especially in the progression of disease.

摘要

越来越多的证据表明,免疫失调在骨肉瘤(OS)的发展中起关键作用。程序性死亡1(PD-1)是一种在活化和耗竭的T细胞上表达的表面受体,其与配体结合后介导T细胞抑制。关于PD-1与OS的研究仍然极为有限。在此,我们研究了PD-1是否参与OS的发展。通过流式细胞术检测了56例OS患者和42例健康对照外周血CD4+和CD8+T细胞上PD-1的表达。数据显示,OS患者外周血CD4+和CD8+T细胞上PD-1的百分比均显著上调(分别为p<0.001和p<0.001)。不同肿瘤部位的患者PD-1水平无明显差异。然而,有转移的患者CD4+T细胞上的PD-1水平显著高于无转移的患者(p<0.001)。此外,CD4+T细胞上的PD-1表达在III期开始增加,而CD8+T细胞上的PD-1表达在II期开始增加。另外,观察到发生病理性骨折的患者CD4+和CD8+T细胞上的PD-1均升高。这些数据表明,PD-1参与了OS的发病机制,尤其是在疾病进展过程中。

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