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通过同种异体线粒体转移增强 NK 细胞的抗癌能力

英文原题:Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer.

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Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer.

PubMed 2023/06/17(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

体外培养至少2周才能产生足够的自然杀伤(NK)细胞用于免疫治疗,而NK细胞是血液恶性肿瘤治疗中的关键效应细胞。线粒体损伤和碎片化会降低NK细胞的免疫监视能力。

因此,我们假设将健康线粒体转移至NK细胞可增强其抗癌效果。将从WRL-68细胞中分离的同种异体健康线粒体转移至NK细胞。

我们通过分析特异性裂解和释放的细胞毒性颗粒,评估了NK细胞的增殖能力、细胞周期以及对多种癌症细胞类型的细胞毒性能力。确定了转移的同种异体线粒体残留与NK细胞功能之间的关系。线粒体转移后,NK细胞增殖率比对照细胞高1.2倍。与K562细胞共培养时,经线粒体处理的NK细胞分泌的颗粒酶B、穿孔素和IFN- 分别高出2.7倍、4.1倍和5倍。对多种实体癌细胞的特异性裂解增加了1.3-1.6倍。

然而,一旦同种异体线粒体被清除,NK细胞活性恢复到线粒体转移前的水平。富含线粒体的NK细胞有潜力作为一种新型实体癌治疗剂,且无需体外细胞因子诱导培养。

展开英文摘要原文

An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity.

Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells.

We evaluated NK cells' proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined.

After mitochondrial transfer, the NK cell proliferation rate was 1. 2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2. 7-, 4. 1-, and 5-fold higher amount of granzyme B, perforin, and IFN- , respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1. 3-1. 6-fold.

However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture.

论文信息

作者
Kim SH、Kim MJ、Lim M、Kim J、Kim H、Yun CK、Yoo YJ、Lee Y
单位
Department of Biotechnology, CHA University, Seongnam 13488, Republic of Korea.South Korea
期刊
Cancers2023 Jun 17
原文标识
PubMed 37370835 · DOI 10.3390/cancers15123225