Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma.

Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma.
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肾细胞癌患者中偏斜的T-helper(Th)1/2和Th17/T调节细胞平衡。

DOI:
10.3892/mmr.2014.2778
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发表时间:
2015-02
影响因子:
3.4
通讯作者:
Rong R
Rong R
中科院分区:
医学4区
文献类型:
--
作者:
Li L;Yang C;Zhao Z;Xu B;Zheng M;Zhang C;Min Z;Guo J;Rong R

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CD 4 + T细胞亚群的特征反映了免疫状态,并在维持肿瘤发生和稳态方面具有重要意义。为探讨肾细胞癌(RCC)患者辅助性T细胞(Th)1、Th 2、Th 17和调节性T细胞(Treg)平衡的变化,本研究对131例RCC患者和36例健康志愿者进行了研究。采用流式细胞术分析检测外周血中CD 4 + T-bet+细胞、CD 4+加塔结合蛋白3+细胞、CD 4 + RAR相关孤儿受体γt+细胞、CD 4 + CD 25 hi CD 127 lo CD 45 RA −细胞和CD 4 + CD 25 hi CD 127 lo CD 45 RA+细胞的数量,分别定义为Th 1、Th 2、Th 17、活化和幼稚Treg细胞。此外,使用免疫组织化学检查肿瘤浸润叉头盒P3(Foxp 3)+细胞。与健康志愿者相比,RCC患者外周血Th 1、活化和幼稚Treg细胞百分比明显下降,而Th 2和Th 17细胞百分比增加。特别是,随着肿瘤分期和分级的进展,外周血中Th 1、活化和幼稚Treg细胞的水平降低;然而,Th 2和Th 17细胞的水平升高。此外,肿瘤浸润Foxp 3+细胞的数量随着肿瘤分期的增加而增加。这些结果表明,在肾细胞癌(RCC)患者的外周血中,Th 1和Th 2细胞的平衡偏向于Th 2分布,而Th 17和Treg细胞的平衡偏向于Th 17分布,并且Treg细胞被募集到肿瘤部位。因此,在RCC患者中观察到功能失调的宿主抗肿瘤免疫,具有偏斜的Th 1/Th 2和Th 17/Treg平衡。
The characterization of CD4+ T-cell subsets reflects the immune status and is important in the maintenance of tumorigenesis and homeostasis. To identify changes in the balance of T helper (Th)1, Th2, Th17 and regulatory T cells (Treg) in individuals with renal cell carcinoma (RCC), the present study investigated a total of 131 patients with RCC and 36 healthy volunteers. The number of CD4+ T-bet+ cells, CD4+ GATA binding protein 3+ cells, CD4+ RAR-related orphan receptor γt+ cells, CD4+ CD25hi CD127lo CD45RA− cells and CD4+ CD25hi CD127lo CD45RA+ cells, defined as Th1, Th2, Th17, activated and naïve Treg cells, respectively, were detected in the peripheral blood using flow cytometric analysis. In addition, tumor-infiltrating forkhead box P3 (Foxp3)+ cells were examined using immunohistochemistry. Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased. In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased. Furthermore, the number of tumor-infiltrating Foxp3+ cells increased with increasing tumor stage. These results demonstrated that the balance of Th1 and Th2 cells was skewed towards the Th2 profile and the balance of Th17 and Treg cells was skewed towards the Th17 profile in the peripheral blood of patients with renal cell carcinoma (RCC) and Treg cells were recruited to the tumor sites. Therefore, dysfunctional host anti-tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.
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