GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer.
GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer.
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GARP 与肿瘤浸润 T 细胞相关并预测胃癌的结果
DOI：
10.3389/fimmu.2021.660397
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发表时间：
2021
影响因子：
7.3
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Jiang S;Zhang Y;Zhang X;Lu B;Sun P;Wu Q;Ding X;Huang J
接受免疫微环境(TME)在肿瘤进展中的关键作用使我们能够识别免疫治疗靶点并开发新的治疗方法。糖蛋白A重复序列占优势(GARP)在维持调节性T细胞(Treg)介导的免疫耐受中起重要作用。GARP在胃癌TME中的作用仍值得探讨。我们调查了来自癌症基因组图谱和基因表达总览的公开基因组数据集，以分析GARP的可能作用及其与胃癌TME的关系。以荧光为基础的多重免疫组织化学和免疫组织化学方法检测一系列组织芯片中的T细胞免疫信号，以验证GARP在TME中的价值。我们初步发现GARP在胃癌细胞中表达上调，并检测到不同程度的免疫细胞浸润和免疫检查点表达。基因表达谱显示GARP的表达与胃癌的TME有关。GARP上调通常伴随FOXP3+Treg和CD4+T细胞的浸润增加。胃癌组织中GARP的表达与CTLA-4、PD-L1的表达呈正相关。COX回归分析和诺模图强调，GARP或GARP+CD4+T细胞可以很好地预测总体生存率较差的可能性。综上所述，这项研究强调了GARP在调节生存和肿瘤浸润性T细胞方面的潜在作用。此外，CD4+T细胞免疫信号在预后中的作用可能具有临床意义，从而为免疫治疗方法提供了新的思路。
Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The impact of GARP in TME of gastric cancer is still worth exploring. We investigated public genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus to analyze the possible role of GARP and its relationship with TME of gastric cancer. Fluorescence-based multiplex immunohistochemistry and immunohistochemistry for T-cell immune signatures in a series of tissue microarrays were used to validate the value of GARP in the TME. We initially found that GARP expression was upregulated in gastric carcinoma cells, and diverse levels o3f immune cell infiltration and immune checkpoint expression were detected. Gene expression profiling revealed that GARP expression was related to the TME of gastric cancer. GARP upregulation was usually accompanied by increased FOXP3+ Treg and CD4+ T cell infiltration. In addition, GARP expression had positive relationships with CTLA-4 and PD-L1 expression in gastric cancer. Cox regression analysis and a nomogram highlighted that the probability of poor overall survival was predicted well by GARP or GARP+CD4+ T cell. Taken together, this research underlines the potential effect of GARP in regulating survival and tumor-infiltrating T-cells. In addition, the function of CD4+ T cell immune signatures in the prognosis can be clinically meaningful, thereby providing a new idea for the immunotherapeutic approach.
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影响因子：
--
作者：
Arasanz H;Gato-Cañas M;Zuazo M;Ibañez-Vea M;Breckpot K;Kochan G;Escors D
通讯作者：
Escors D
胃癌的生物标志物：早期诊断和预后的进展（综述）。
影响因子：
2.9
作者：
Jin Z;Jiang W;Wang L
通讯作者：
Wang L
影响因子：
11.2
作者：
Metelli A;Wu BX;Fugle CW;Rachidi S;Sun S;Zhang Y;Wu J;Tomlinson S;Howe PH;Yang Y;Garrett-Mayer E;Liu B;Li Z
通讯作者：
Li Z
影响因子：
17.1
作者：
Cuende, Julia;Lienart, Stephanie;Lucas, Sophie
通讯作者：
Lucas, Sophie
影响因子：
15.9
作者：
Fakih, Marwan;Ouyang, Ching;Lee, Peter P.
通讯作者：
Lee, Peter P.