T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer

作者：Jianfeng Liu, Si‐Rui Ma, Liang Mao, Lin‐Lin Bu, Guang‐Tao Yu, Yicun Li, Cong‐Fa Huang, Wei‐Wei Deng, Ashok B. Kulkarni, Wen‐Feng Zhang, Zhi‐Jun Sun · 发表于：Molecular Oncology · 年份：2017 · DOI：10.1002/1878-0261.12029 · 被引用次数：82 · 研究领域：Galectins and Cancer Biology、Macrophage Migration Inhibitory Factor、Peptidase Inhibition and Analysis

T‐cell immunoglobulin mucin 3 ( TIM 3) contributes to immune suppression during progression of many cancers, but the precise role of TIM 3 in head and neck squamous cell carcinoma ( HNSCC ) is not clearly understood. In this study, we report that TIM 3 expression was significantly up‐regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM 3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD 8 + T cells and CD 11b + CD 33 + myeloid‐derived suppressor cells ( MDSC s) in human HNSCC , and found that their expression was positively correlated with TIM 3 expression. To determine the underlying mechanism of TIM 3 in immune response during HNSCC progression, we utilized the Tgfbr1/Pten 2c KO HNSCC mouse model with TIM 3 overexpression. Treatment with anti‐ TIM 3 monoclonal antibody effectively suppressed tumor growth through restoring effector T‐cell function by targeting CD 4 + TIM 3 + cells and CD 8 + TIM 3 + cells and decreasing MDSC s. Our findings demonstrate TIM 3 expression in patients with HNSCC and suggest anti‐ TIM 3 immunotherapy as a novel therapeutic approach for effective treatment of HNSCC .