Localized Imaging of Programmed Death-Ligand 1 on Individual Tumor-Derived Extracellular Vesicles for Prediction of Immunotherapy Response.
Localized Imaging of Programmed Death-Ligand 1 on Individual Tumor-Derived Extracellular Vesicles for Prediction of Immunotherapy Response.
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程序性死亡配体 1 在个体肿瘤衍生的细胞外囊泡上的局部成像，用于预测免疫治疗反应。
DOI：
10.1021/acsnano.3c05799
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发表时间：
2023-10
期刊：
影响因子：
17.1
通讯作者：
Junli Zhang;Mengting Guan;Min Lv;Yingying Liu;Hongling Zhang;Zhenzhong Zhang;Kaixiang Zhang
中科院分区：
文献类型：
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作者：
Junli Zhang;Mengting Guan;Min Lv;Yingying Liu;Hongling Zhang;Zhenzhong Zhang;Kaixiang Zhang
肿瘤源性小细胞外囊泡（EV）上的程序性死亡配体1（PD-L1）是预测免疫治疗反应的生物标志物。然而，常规的批量测量很难分析PD-L1在个体肿瘤源性EV上的表达。本文中，开发了用于肿瘤衍生的个体EV PD-L1（LITIE）的局部成像的方法。在该测定中，将血浆中的EV直接捕获在生物芯片上。然后使用脂质体介导的膜融合策略对EV中的miR-21进行成像，以将miR-21阳性EV与整个EV群体区分开。随后，应用引物交换反应（PER）以产生局部和放大的荧光信号，用于在鉴定的肿瘤衍生EV上成像PD-L1。当应用于临床样本检测时，LITIE检测可以有效区分乳腺癌患者与健康供体或良性肿瘤患者。有趣的是，在小鼠黑色素瘤模型中，LITIE测定显示出甚至在药物治疗之前预测免疫治疗反应的能力。因此，我们认为测量个体肿瘤源性EV PD-L1的策略可以作为筛选适合免疫治疗的临床应答者的替代方法。
Programmed death-ligand 1 (PD-L1) on tumor-derived small extracellular vesicles (EVs) is a biomarker for prediction of the immunotherapy response. However, conventional bulk measurement can hardly analyze the expression of PD-L1 on individual tumor-derived EVs. Herein, a method for localized imaging of tumor-derived individual EVs PD-L1 (LITIE) is developed. In this assay, EVs in plasma were directly captured on a biochip. Then the liposome-mediated membrane fusion strategy was used to image miR-21 in EVs to discriminate miR-21-positive EVs from the whole EVs populations. Subsequently, the primer exchange reaction (PER) is applied to generate localized and amplified fluorescent signals for imaging PD-L1 on identified tumor-derived EVs. When applied in clinical sample tests, the LITIE assay could effectively distinguish breast cancer patients from healthy donors or patients with benign tumors. Interestingly, in a mice melanoma model, the LITIE assay showed the ability to predict immunotherapy response even before drug treatment. Thus, we think the strategy of measuring individual tumor-derived EVs PD-L1 could serve as an alternative way for screening clinical responders suitable for immunotherapy.