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通过1024份样本对胶质瘤中TIM-3进行分子和临床特征分析。

Molecular and clinical characterization of TIM-3 in glioma through 1,024 samples.

作者信息

Li Guanzhang, Wang Zheng, Zhang Chuanbao, Liu Xing, Cai Jinquan, Wang Zhiliang, Hu Huimin, Wu Fan, Bao Zhaoshi, Liu Yanwei, Zhao Liang, Liang Tingyu, Yang Fan, Huang Ruoyu, Zhang Wei, Jiang Tao

机构信息

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Chinese Glioma Genome Atlas Network (CGGA).

出版信息

Oncoimmunology. 2017 Jul 28;6(8):e1328339. doi: 10.1080/2162402X.2017.1328339. eCollection 2017.

Abstract

: Researches on immunotherapy of glioma has been increasing exponentially in recent years. However, autoimmune-like side effects of current immune checkpoint blockade hindered the clinical application of immunotherapy in glioma. The discovery of the TIM-3, a tumor-specific immune checkpoint, has shed a new light on solution of this dilemma. We aimed at investigating the role of TIM-3 at transcriptome level and its relationship with clinical practice in glioma. : A cohort of 325 glioma patients with RNA-seq data from Chinese Glioma Genome Atlas (CGGA project) was analyzed, and the results were well validated in TCGA RNA-seq data of 699 gliomas. R language was used as the main tool for statistical analysis and graphical work. : TIM-3 was enriched in glioblastoma (the most malignant glioma) and IDH-wildtype glioma. TIM-3 can act as a potential marker for mesenchymal molecular subtype according to TCGA transcriptional classification scheme in glioma. TIM-3 was closely related to immune functions in glioma, especially T cell mediated immune response to tumor cell and T cell mediated cytotoxicity directed against tumor cell target. Moreover, TIM-3 and PD-L1 played almost exactly the same inflammatory activation functions in glioma. Clinically, high expression of TIM-3 was an independent indicator of poor prognosis. : The expression of TIM-3 is closely related to the pathology and molecular pathology of glioma. Meanwhile, in glioma TIM-3 plays a specific role in T cell tumor immune response. Therefore, TIM-3 is a promising target for immunotherapeutic strategies, providing an alternative treatment when glioma gains resistance to antibodies of PD-1/PD-L1.

摘要

近年来,关于胶质瘤免疫治疗的研究呈指数级增长。然而,当前免疫检查点阻断的自身免疫样副作用阻碍了免疫治疗在胶质瘤中的临床应用。肿瘤特异性免疫检查点TIM-3的发现为解决这一困境带来了新的曙光。我们旨在研究TIM-3在转录组水平上的作用及其与胶质瘤临床实践的关系。:分析了来自中国胶质瘤基因组图谱(CGGA项目)的325例有RNA测序数据的胶质瘤患者队列,结果在699例胶质瘤的TCGA RNA测序数据中得到了很好的验证。R语言用作统计分析和图形工作的主要工具。:TIM-3在胶质母细胞瘤(最恶性的胶质瘤)和异柠檬酸脱氢酶(IDH)野生型胶质瘤中富集。根据胶质瘤的TCGA转录分类方案,TIM-3可作为间充质分子亚型的潜在标志物。TIM-3与胶质瘤中的免疫功能密切相关,尤其是T细胞介导的对肿瘤细胞的免疫反应和T细胞介导的针对肿瘤细胞靶标的细胞毒性。此外,TIM-3和程序性死亡受体配体1(PD-L1)在胶质瘤中发挥几乎完全相同的炎症激活功能。临床上,TIM-3高表达是预后不良的独立指标。:TIM-3的表达与胶质瘤的病理和分子病理密切相关。同时,在胶质瘤中TIM-3在T细胞肿瘤免疫反应中发挥特定作用。因此,TIM-3是免疫治疗策略的一个有前景的靶点,当胶质瘤对PD-1/PD-L1抗体产生耐药性时提供了一种替代治疗方法。

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