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

• Published in: Oncoimmunology 2017-08, Vol.6 (8), p.e1328339-e1328339
• Main 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
• Format: Article
• Language: English
• Subjects: Glioma; immune response; inflammatory activation; Original Research; prognosis; TIM-3
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2017.1328339

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.