Extracellular Vesicles From the Human Natural Killer Cell Line NK3.3 Have Broad and Potent Anti-Tumor Activity.
Extracellular Vesicles From the Human Natural Killer Cell Line NK3.3 Have Broad and Potent Anti-Tumor Activity.
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来自人类天然杀手细胞系NK3.3的细胞外囊泡具有广泛而有效的抗肿瘤活性。
DOI：
10.3389/fcell.2021.698639
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发表时间：
2021
影响因子：
5.5
通讯作者：
Kornbluth J
中科院分区：
文献类型：
--
作者：
Cochran AM;Kornbluth J
自然杀伤 (NK) 细胞是免疫功能的关键介质，负责快速破坏肿瘤细胞。它们主要通过释放含有强效溶细胞分子的颗粒来杀死。 NK 细胞还在膜结合的外泌体和微囊泡（统称为细胞外囊泡 (EV)）内释放这些分子。在这里，我们报告了从 NK3.3 细胞中分离出的 EV 的特征和抗肿瘤功能，NK3.3 细胞是一种充分描述的克隆正常人 NK 细胞系。我们发现 NK3.3 EV 含有溶细胞分子穿孔素、颗粒酶 A 和 B、颗粒溶素以及一系列常见的 EV 蛋白。我们之前报道过 E3 泛素连接酶，即自然杀伤细胞裂解相关分子 (NKLAM)，定位于 NK 颗粒，对于最大程度地杀伤 NK 至关重要。在这里，我们展示了它存在于 NK3.3 EV 的膜中。 NK3.3 衍生的 EV 还携带多种 RNA，包括与抗肿瘤活性相关的 miRNA。我们证明 NK3.3 EV 抑制一系列造血和非造血肿瘤细胞系的增殖并诱导 caspase 介导的细胞凋亡和细胞死亡。这种作用是肿瘤细胞特异性的；正常细胞不受 EV 治疗的影响。由于NK3.3 EV源自健康供体并且能够大量扩增，因此有潜力成为一种有效、安全和通用的免疫治疗剂。
Natural killer (NK) cells are critical mediators of immune function, responsible for rapid destruction of tumor cells. They kill primarily through the release of granules containing potent cytolytic molecules. NK cells also release these molecules within membrane-bound exosomes and microvesicles – collectively known as extracellular vesicles (EV). Here we report the characterization and anti-tumor function of EVs isolated from NK3.3 cells, a well described clonal normal human NK cell line. We show that NK3.3 EVs contain the cytolytic molecules perforin, granzymes A and B, and granulysin, and an array of common EV proteins. We previously reported that the E3 ubiquitin ligase, natural killer lytic-associated molecule (NKLAM), is localized to NK granules and is essential for maximal NK killing; here we show it is present in the membrane of NK3.3 EVs. NK3.3-derived EVs also carry multiple RNA species, including miRNAs associated with anti-tumor activity. We demonstrate that NK3.3 EVs inhibit proliferation and induce caspase-mediated apoptosis and cell death of an array of both hematopoietic and non-hematopoietic tumor cell lines. This effect is tumor cell specific; normal cells are unaffected by EV treatment. By virtue of their derivation from a healthy donor and ability to be expanded to large numbers, NK3.3 EVs have the potential to be an effective, safe, and universal immunotherapeutic agent.
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影响因子：
3.7
作者：
Comerci CJ;Mace EM;Banerjee PP;Orange JS
通讯作者：
Orange JS
影响因子：
4
作者：
Lawrence DW;Willard PA;Cochran AM;Matchett EC;Kornbluth J
通讯作者：
Kornbluth J
影响因子：
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作者：
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通讯作者：
Moretta, Lorenzo
影响因子：
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作者：
De Colvenaer, Veerle;Taveirne, Sylvie;Leclercq, Georges
通讯作者：
Leclercq, Georges
影响因子：
7.4
作者：
Kubiczkova L;Sedlarikova L;Hajek R;Sevcikova S
通讯作者：
Sevcikova S