Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies
Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies
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DOI：
10.1021/acsnano.9b07326
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发表时间：
2020-01-01
期刊：
影响因子：
17.1
通讯作者：
Bardhan, Rizia
中科院分区：
文献类型：
--
作者：
Ou, Yu-Chuan;Wen, Xiaona;Bardhan, Rizia
免疫标记物程序性细胞死亡蛋白1(PD-I)的过度表达及其与其配体PD-L1的结合参与了分化簇8(+)(CD8(+))T细胞的功能损伤，促进了肿瘤的进展。然而，PD-LI表达的异质性和基于活检的检测的变异性使得目前的方法在预测PD-L1状态方面不准确。因此，PD-LI筛查本身并不能预测患者对治疗的反应，这促使我们同时检测参与免疫调节的多个免疫标记物。在这里，我们开发了多模式探针，免疫活性金纳米星(IGN)，可以在体内同时准确检测PD-L1(+)肿瘤细胞和CD8(+)T细胞，超越了目前免疫成像技术的局限性。IGN将正电子发射断层扫描的全身成像与拉曼光谱的高灵敏度和多路复用相结合，能够动态跟踪这两种免疫标记物。免疫球蛋白还监测用PD-L1和CD137联合激动剂治疗的小鼠对免疫治疗的反应，并区分对治疗有反应者和无反应者。我们的结果显示，一种多功能纳米级探针具有单独使用这两种方法无法实现的能力，允许多重免疫肿瘤分析，这对预测免疫治疗的早期反应至关重要。
The overexpression of immunomarker programmed cell death protein 1 (PD-I) and engagement of PD-1 to its ligand, PD-L1, are involved in the functional impairment of cluster of differentiation 8(+) (CD8(+)) T cells, contributing to cancer progression. However, heterogeneities in PD-LI expression and variabilities in biopsy-based assays render current approaches inaccurate in predicting PD-L1 status. Therefore, PD-LI screening alone is not predictive of patient response to treatment, which motivates us to simultaneously detect multiple immunomarkers engaged in immune modulation. Here, we have developed multimodal probes, immunoactive gold nanostars (IGNs), that accurately detect PD-L1(+) tumor cells and CD8(+) T cells simultaneously in vivo, surpassing the limitations of current immunoimaging techniques. IGNs integrate the whole-body imaging of positron emission tomography with high sensitivity and multiplexing of Raman spectroscopy, enabling the dynamic tracking of both immunomarkers. IGNs also monitor response to immunotherapies in mice treated with combinatorial PD-L1 and CD137 agonists and distinguish responders from those nonresponsive to treatment. Our results showed a multifunctional nanoscale probe with capabilities that cannot be achieved with either modality alone, allowing multiplexed immunologic tumor profiling critical for predicting early response to immunotherapies.