Expression of GARP Is Increased in Tumor-Infiltrating Regulatory T Cells and Is Correlated to Clinicopathology of Lung Cancer Patients.
Expression of GARP Is Increased in Tumor-Infiltrating Regulatory T Cells and Is Correlated to Clinicopathology of Lung Cancer Patients.
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肿瘤浸润调节性 T 细胞中 GARP 表达增加，且与肺癌患者的临床病理相关
DOI：
10.3389/fimmu.2017.00138
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发表时间：
2017
影响因子：
7.3
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Jin H;Sun L;Tang L;Yu W;Li H
调节性T细胞(Tregs)是一种免疫抑制T细胞，在免疫稳态中发挥重要作用。已有多个标记与Tregs的特性和功能相关联。最近发现，糖蛋白A重复占优势(GARP)是一种含有丰富亮氨酸重复序列的跨膜蛋白，它在激活的Tregs表面高表达。GARP通过激活和分泌转化生长因子β来维持Treg的调节功能和动态平衡。在本研究中，我们研究了肺癌患者外周血和肿瘤组织中GARP的表达。分析Tregs上GARP的比例和表达水平与肺癌患者临床病理因素的关系。结果表明，在肺癌患者的肿瘤组织中，Tregs中GARP的表达增加，并与淋巴结转移、远处转移和临床分期有关。此外，早期患者的浸润性Tregs的GARP表达高于晚期患者，提示GARP可能是一个早期预后的生物标志物。体外共培养研究表明，人肺癌细胞系可能通过某种机制诱导Tregs中GARP的表达。总体而言，本研究证明了GARP在Tregs定义和癌症免疫治疗中的潜在价值。
Regulatory T cells (Tregs) are immunosuppressive T cells that play an important role in immune homeostasis. Multiple markers have been associated with the characterization, as well as function of Tregs. Recently, glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine-rich repeats, has been found to be highly expressed on the surface of activated Tregs. GARP maintains Tregs’ regulatory function and homeostasis through the activation and secretion of transforming growth factor β. In this study, we investigated the expression of GARP in Tregs from the peripheral blood (PB) and tumor tissues of lung cancer patients. The association between the proportion and expression level of GARP on Tregs and the clinicopathological factors of lung cancer patients was also analyzed. Results showed that in the tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and was associated with lymph node metastasis, distant metastasis, and clinical stage. Furthermore, the infiltrating Tregs from early stage patients exhibited higher GARP expression than that from advanced cancer patients, which indicated that GARP might be an early prognostic biomarker. In vitro coculture studies demonstrated that human lung cancer cell lines might induce the expression of GARP in Tregs by certain mechanisms. Overall, this research demonstrated the potential value of GARP in Tregs definition and cancer immunotherapy.