EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer.
EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer.
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DOI：
10.3390/ijms18040878
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发表时间：
2017-04-20
影响因子：
5.6
通讯作者：
Coy JF
中科院分区：
文献类型：
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作者：
Coy JF
单核细胞表位检测（EDIM）代表了利用先天免疫系统的液体活检。活化的单核细胞（巨噬细胞）吞噬来自全身（包括实体组织）的不需要的细胞/细胞碎片。当它们返回血液时，巨噬细胞可用于生物标志物的非侵入性检测，从而提供高灵敏度和特异性，因为生物标志物的细胞内存在是由于先天免疫应答。血液的流式细胞术分析能够检测巨噬细胞和吞噬的细胞内生物标志物。为了建立泛癌症测试，已经开发了两种基本生物物理机制的生物标志物。DNaseX/Apo 10蛋白表位是具有异常凋亡和增殖的肿瘤细胞的特征。转酮醇酶样1（Transketolase-like 1，TKTL 1）是无氧葡萄糖代谢（瓦尔堡效应）的标志物，其伴随着侵袭性生长/转移，并且对根治性和凋亡诱导疗法具有抗性。血液巨噬细胞中Apo 10和TKTL 1的检测允许对前列腺癌、乳腺癌和口腔鳞状细胞癌进行敏感性（95.8%）和特异性（97.3%）检测。由于TKTL 1代表一种药物靶点，因此基于EDIM的TKTL 1检测能够使用维生素衍生物羟硫胺素或苯氧硫胺素进行靶向癌症治疗。
Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10 protein epitope is a characteristic of tumor cells with abnormal apoptosis and proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose metabolism (Warburg effect), which is concomitant with invasive growth/metastasis and resistant to radical and apoptosis inducing therapies. The detection of Apo10 and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%) detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1 represents a drugable target, the EDIM based detection of TKTL1 enables a targeted cancer therapy using the vitamin derivatives oxythiamine or benfo-oxythiamine.