Wei Bo, Wang Le, Zhao Xingli, Du Chao, Guo Yongchuan, Sun Zhigang
The Second Division of Neurosurgery, The China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin, 130033, China.
Tumour Biol. 2014 Apr;35(4):2923-9. doi: 10.1007/s13277-013-1376-9. Epub 2013 Dec 28.
Glioma is the most common primary brain tumor. 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. In the current study, we investigated the expression of PD-1 on peripheral CD4+ and CD8+ T cells in glioma patients. Percentage of PD-1+ cells was measured by flow cytometry in 86 glioma cases and 62 healthy controls. Results showed that PD-1 expression was significantly increased in both peripheral CD4+ and CD8+ T cells in glioma (p < 0.001 and p < 0.001, respectively). When comparing PD-1 level in glioma patients with different histological types, patients with astrocytomas revealed clearly higher proportion of PD-1 on CD4+ T cells than those with oligodendrogliomas (p < 0.001), ependymomas (p < 0.001), or pilocytic astrocytomas (p < 0.001). Also, patients with the highest tumor grade (IV) demonstrated the most elevated expression of PD-1 on both CD4+ and CD8+ T cells. Interestingly, cases with tumor grade III and IV had downregulated PD-1 level on peripheral CD4+ T cells after surgery, whereas only grade IV patients showed decreased proportion of PD-1 on CD8+ T cells after treatment. In addition, no correlation between PD-1 expression and progression to secondary glioblastoma was observed. These data suggested PD-1 may act as a positive regulator in the pathogenesis and progression of glioma.
胶质瘤是最常见的原发性脑肿瘤。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。在本研究中,我们调查了胶质瘤患者外周血CD4+和CD8+T细胞上PD-1的表达情况。通过流式细胞术检测了86例胶质瘤病例和62例健康对照中PD-1+细胞的百分比。结果显示,胶质瘤患者外周血CD4+和CD8+T细胞中的PD-1表达均显著增加(分别为p<0.001和p<0.001)。在比较不同组织学类型的胶质瘤患者的PD-1水平时,星形细胞瘤患者CD4+T细胞上的PD-1比例明显高于少突胶质细胞瘤患者(p<0.001)、室管膜瘤患者(p<0.001)或毛细胞型星形细胞瘤患者(p<0.001)。此外,肿瘤分级最高(IV级)的患者在CD4+和CD8+T细胞上的PD-1表达均最高。有趣的是,III级和IV级肿瘤患者术后外周血CD4+T细胞上的PD-1水平下调,而只有IV级患者在治疗后CD8+T细胞上的PD-1比例下降。此外,未观察到PD-1表达与继发性胶质母细胞瘤进展之间的相关性。这些数据表明,PD-1可能在胶质瘤的发病机制和进展中起正向调节作用。