On-Chip Biogenesis of Circulating NK Cell-Derived Exosomes in Non-Small Cell Lung Cancer Exhibits Antitumoral Activity.
On-Chip Biogenesis of Circulating NK Cell-Derived Exosomes in Non-Small Cell Lung Cancer Exhibits Antitumoral Activity.
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非小细胞肺癌中NK细胞来源的外切体在芯片上的生物发生显示出抗肿瘤活性。
DOI：
10.1002/advs.202003747
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Nagrath S
中科院分区：
文献类型：
--
作者：
Kang YT;Niu Z;Hadlock T;Purcell E;Lo TW;Zeinali M;Owen S;Keshamouni VG;Reddy R;Ramnath N;Nagrath S
由于自然杀伤（NK）细胞和癌细胞之间的识别不需要抗原呈递，因此正在积极研究NK细胞用于快速发展的癌症免疫疗法中的过继细胞疗法。除了利用NK细胞外，最近的研究表明，来源于NK细胞的外来体也表现出抗肿瘤特性。此外，与NK细胞相比，这些NK细胞衍生的外泌体表现出更高的稳定性、更大的修饰潜力和更低的免疫原性。因此，允许高度敏感和特异性分离NK细胞和NK细胞衍生的外泌体的技术可以在未来实现个性化的NK介导的癌症治疗。在这里，提出了一种新的微流体系统来收集患者特异性NK细胞和NK外泌体的芯片生物发生。在一个非小细胞肺癌（NSCLC）患者的小队列中，分离了NK细胞和循环肿瘤细胞（CTC），发现NSCLC患者与健康供体相比具有较高数量的NK和NK-exosomes，并且这些浓度分别显示出与血源性CTC数量正相关和负相关的趋势。进一步证明了从NK-氧化石墨烯芯片收获的NK-外来体对CTC表现出细胞毒性作用。这种多功能系统预计将用于患者特异性NK免疫治疗，沿着CTC，用于潜在的预后/诊断应用。自然杀伤（NK）细胞是具有在没有抗原呈递的情况下破坏癌细胞的能力的淋巴细胞。与NK细胞相比，NK细胞衍生的外泌体表现出更高的稳定性、更大的修饰潜力和更低的免疫原性。在这里，提出了一种新的微流体系统，用于收集患者特异性NK细胞和NK外泌体的芯片上生物发生，用于NK外泌体的诊断和治疗用途。
As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studies have shown that exosomes derived from NK cells also exhibit antitumor properties. Furthermore, these NK cell‐derived exosomes exhibit higher stability, greater modification potentials and less immunogenicity compared to NK cells. Therefore, technologies that allow highly sensitive and specific isolation of NK cells and NK cell‐derived exosomes can enable personalized NK‐mediated cancer therapeutics in the future. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes is proposed. In a small cohort of non‐small cell lung cancer (NSCLC) patients, both NK cells and circulating tumor cells (CTCs) were isolated, and it is found NSCLC patients have high numbers of NK and NK‐exosomes compared with healthy donors, and these concentrations show a trend of positive and negative correlations with bloodborne CTC numbers, respectively. It is further demonstrated that the NK‐exosomes harvested from NK‐graphene oxide chip exhibit cytotoxic effect on CTCs. This versatile system is expected to be used for patient‐specific NK‐based immunotherapies along with CTCs for potential prognostic/diagnostic applications. Natural killer (NK) cells are lymphocytes that have the ability to destroy cancer cells without antigen presentation. The NK cell‐derived exosomes exhibit higher stability, greater modification potentials, and less immunogenicity compared to NK cells. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes for diagnostic and therapeutic use of NK‐exosomes is proposed.
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