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首页> 外文期刊>British Journal of Cancer >New tools to prevent cancer growth and spread: a ‘Clever’ approach
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New tools to prevent cancer growth and spread: a ‘Clever’ approach

机译:预防癌症生长和传播的新工具:“巧妙”的方法

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Clever-1 (also known as Stabilin-1 and FEEL-1) is a scavenger receptor expressed on lymphatic endothelial cells, sinusoidal endothelial cells and immunosuppressive monocytes and macrophages. Its role in cancer growth and spread first became evident in Stab1 ~(–/–) knockout mice, which have smaller primary tumours and metastases. Subsequent studies in mice and humans have shown that immunotherapeutic blockade of Clever-1 can activate T-cell responses, and that this response is mainly mediated by a phenotypic change in macrophages and monocytes from immunosuppressive to pro-inflammatory following Clever-1 inhibition. Analyses of human cancer cohorts have revealed marked associations between the number of Clever-1-positive macrophages and patient outcome. As hardly any reports to date have addressed the role of Clever-1 in immunotherapy resistance and T-cell dysfunction, we performed data mining using several published cancer cohorts, and observed a remarkable correlation between Clever-1 positivity and resistance to immune checkpoint therapies. This result provides impetus and potential for the ongoing clinical trial targeting Clever-1 in solid tumours, which has so far shown a shift towards immune activation when a particular epitope of Clever-1 is blocked.
机译:聪明-1(也称为stabilin-1和感觉1)是在淋巴内皮细胞,正弦内皮细胞和免疫抑制单核细胞和巨噬细胞上表达的清除剂受体。其在癌症生长和传播中的作用首先在刺激〜(/ - )敲除小鼠中最明显,具有较小的主要肿瘤和转移。在小鼠和人体中的后续研究表明,巧妙-1的免疫治疗阻断可以激活T细胞反应,并且这种反应主要由巨噬细胞和单核细胞中的表型变化介导,从免疫抑制到巧妙 - 1抑制后促炎。人类癌症队列的分析揭示了聪明-1阳性巨噬细胞和患者结果的数量之间的显着关联。正如迄今为止的任何报告都已经解决了聪明-1在免疫疗法抗性和T细胞功能障碍中的作用,我们使用几个公布的癌症队列进行了数据挖掘,并观察到巧妙-1阳性与免疫检查点疗法之间的显着相关性。该结果提供了靶向临床试验的动力和潜力,该临床试验在实体肿瘤中均有肿瘤,这对于智能-1的特定表位被阻断时,目前已经显示出朝向免疫激活的转变。

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