Tim-3 expression predicts the abnormal innate immune status and poor prognosis of glioma patients
Tim-3 expression predicts the abnormal innate immune status and poor prognosis of glioma patients
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Tim-3表达预测胶质瘤患者先天免疫状态异常和不良预后
DOI：
10.1016/j.cca.2017.11.022
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发表时间：
2018-01-01
影响因子：
5
通讯作者：
Li, Xingang
中科院分区：
文献类型：
--
作者：
Li, Xueen;Wang, Bo;Li, Xingang
恶性胶质瘤是最常见和最具破坏性的原发脑肿瘤，严重影响人类健康，复发风险高，生存期短。近年来，免疫学机制的开发为开发脑胶质瘤发病机制的新治疗策略提供了新的思路。TIM-3是T细胞免疫球蛋白和粘蛋白结构域家族的成员，通过调节免疫细胞的活性和功能，参与包括肿瘤在内的多种疾病。本研究检测了脑胶质瘤患者外周血中天然免疫细胞TIM-3的表达，并分析其与临床指标的相关性。我们发现脑胶质瘤患者外周血中CD3(-)、CD56(+)NK细胞数量明显减少。脑胶质瘤患者外周血CD3(-)、CD56(+)、NK细胞和CD14(+)单核细胞TIM-3的表达均高于正常对照组。TIM-3(+)NK细胞分泌干扰素-r的能力降低，而TIM-3(+)单核细胞表现为M2样表型。重要的是，NK细胞和单核细胞上TIM-3水平与Ki-67(+)肿瘤细胞比例呈正相关。此外，单核细胞TIM-3(+)比例高的患者复发或死亡的风险也很高。我们的工作对脑胶质瘤的先天免疫机制有了新的认识，并可能为以TIM-3为基础的免疫治疗在脑胶质瘤的临床应用提供新的证据。
Malignant glioma, the most common and devastating primary brain tumor, has serious effects on human health with high risk of recurrence and short survival periods. Recently, the exploitation of immunological mechanisms shed-new lights for developing novel therapeutic strategies for glioma pathogenesis. Tim-3, a member of T cell immunoglobulin and mucin domain family, has been involved in multiple diseases, including tumor, by regulating the viability and function of immunocytes. In the present study, we detected Tim-3 expression on peripheral innate immunocytes from glioma patients and analyzed their correlation with clinical indices. We found that the number of CD3(-) CD56(+) NK cells decreased in glioma patients. Compared with healthy controls, glioma patients had higher Tim-3 expression on peripheral CD3(-) CD56(+) NK cells and CD14(+) monocytes. Tim-3(+) NK cells had decreased capability of IFN-r secretion, while Tim-3(+) monocytes showed a M2-like phenotype. Importantly, Tim-3 level on both NK cells and monocytes positively correlated with the ratio of Ki-67(+) tumor cells. Moreover, patients with high percentage of Tim-3(+) monocytes showed high risk of recurrence or death. Our present work gives new insights into the innate immune mechanisms in glioma and might provide new evidences for the clinical practice of Tim-3-based immunotherapy in glioma.