Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.
Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.
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DOI：
10.1158/0008-5472.can-14-1203
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发表时间：
2014-09-15
期刊：
影响因子：
11.2
通讯作者：
Lowenstein PR
中科院分区：
文献类型：
--
作者：
Baker GJ;Chockley P;Yadav VN;Doherty R;Ritt M;Sivaramakrishnan S;Castro MG;Lowenstein PR
自然杀伤（NK）细胞通过在称为NK免疫监视的过程中破坏转化的靶细胞来防止早期肿瘤形成。然而，恶性脑肿瘤用于破坏这种先天免疫监视的免疫逃逸机制仍不清楚。我们发现恶性胶质瘤细胞通过过表达β-半乳糖苷结合凝集素galectin-1抑制NK免疫监视。相反，半乳糖凝集素-1缺陷的神经胶质瘤细胞可以在抗肿瘤T细胞应答开始之前被宿主NK细胞根除。体外实验表明，半乳糖凝集素-1缺陷型GL 26-Cit神经胶质瘤细胞对NK介导的肿瘤裂解的敏感性是半乳糖凝集素-1表达细胞的约3倍。我们的研究结果表明，半乳糖凝集素-1抑制人类胶质瘤可以提高患者的生存恢复NK免疫监视，可以根除胶质瘤细胞。
Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1 deficient glioma cells could be eradicated by host NK cells prior to the initiation of an anti-tumor T-cell response. In vitro experiments demonstrated that galectin-1 deficient GL26-Cit glioma cells are ~3-fold more sensitive to NK-mediated tumor lysis that galectin-1 expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells.