Molecular and clinical characterization of TIM-3 in glioma through 1, 024 samples. (3rd August 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Oncoimmunology. Volume 6:Number 8(2017)
• Publication Date: 2017-08-03
• Subjects: Glioma -- immune response -- inflammatory activation -- prognosis -- TIM-3; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1328339
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Background : 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. Methods : 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. Results : 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. Conclusion : 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.