Cancer cell intrinsic TIM-3 induces glioblastoma progression
Qing Guo,
Shuai Shen,
Gefei Guan,
Chen Zhu,
Cunyi Zou,
Jingyuan Cao,
Wen Cheng,
Xiaoyan Xu,
Juanhan Yu,
Zhiguo Lin,
Guoli Wang,
Ling Chen,
Peng Cheng,
Anhua Wu
Affiliations
Qing Guo
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China
Shuai Shen
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China
Gefei Guan
Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China
Chen Zhu
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China
Cunyi Zou
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China
Jingyuan Cao
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
Wen Cheng
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China; Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China
Xiaoyan Xu
Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, Liaoning, China
Juanhan Yu
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China
Zhiguo Lin
Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
Guoli Wang
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China
Ling Chen
Department of Neurosurgery, Chinese People’s Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, Beijing, China
Peng Cheng
Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning, China; Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China; Corresponding author
Anhua Wu
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China; Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China; Corresponding author
Summary: Glioblastoma (GBM) is identified to share common signal pathways between glioma and immune cells. Here, we find that T cell immunoglobulin domain and mucin domain protein 3 (TIM-3) is one of the most common co-inhibitory immune checkpoints in GBM shared by tumor and non-tumor cells. Glioma cell-intrinsic TIM-3 is involved in not only regulating malignant behaviors of glioma cells but also inducing macrophage migration and transition to anti-inflammatory/pro-tumorigenic phenotype by a TIM-3/interleukin 6 (IL6) signal. In mechanism, as one of the major regulators of IL6, TIM-3 regulates its expression through activating NF-κB. Blocking this feedback loop by Tocilizumab, an IL6R inhibitor, inhibited the above effects and repressed the tumorigenicity of GBM in vivo. Our work identifies glioma cell-intrinsic functions of TIM-3/IL6 signal mediating the crosstalk feedback loop between glioma cells and tumor-associated macrophages (TAMs). Blocking this feedback loop may provide a novel therapeutic strategy for GBM.
