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NK 细胞来源的细胞外囊泡在三阴性乳腺癌中表现出对整体肿瘤细胞和癌症干细胞的细胞毒性

英文原题:Natural Killer Cell-Derived Extracellular Vesicles Exhibit Cytotoxicity Against Bulk Tumor Cells and Cancer Stem Cells in Triple-Negative Breast Cancer.

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Natural Killer Cell-Derived Extracellular Vesicles Exhibit Cytotoxicity Against Bulk Tumor Cells and Cancer Stem Cells in Triple-Negative Breast Cancer.

PubMed 2026/04/27(内容时间) Nanomaterials (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

三阴性乳腺癌(TNBC)仍然是肿瘤学领域的重大挑战,是女性癌症相关死亡的重要原因。目前的治疗选择,包括化疗、手术、放疗和激素靶向治疗,疗效有限,因此需要探索创新的治疗模式。耐药性的出现和癌症干细胞(CSCs)的持续存在进一步凸显了对新型治疗策略的迫切需求。

在此背景下,NK 细胞来源的细胞外囊泡(NK-EVs)已成为一种有前景的无细胞治疗手段,对癌细胞和CSCs表现出高肿瘤浸润性和细胞毒性。

本研究旨在利用多种临床相关模型,包括患者来源的异种移植瘤,探讨NK-EVs作为TNBC治疗策略的疗效。通路分析表明,NK-EVs通过经典caspase激活强烈诱导凋亡,以及坏死,从而证实了NK-EVs重要的细胞毒性作用。有趣的是,NK-EVs还被发现通过破坏TNBC CSCs的功能和活力来抑制CSCs,且NK-EV处理增加了CSCs和非CSCs中凋亡标志物的表达。通过阐明基于NK-EV的干预措施在TNBC中的治疗疗效和转化潜力,这些发现为针对这一侵袭性乳腺癌亚型的未来免疫治疗策略的开发提供了关键见解。

展开英文摘要原文

Triple-negative breast cancer (TNBC) remains a significant challenge in oncology, contributing to a significant portion of cancer-related deaths among women. Current therapeutic options, including chemotherapy, surgery, radiation, and hormonal targeting therapies, exhibit limited efficacy, necessitating the exploration of innovative treatment modalities.

The emergence of drug resistance and the persistence of cancer stem cells (CSCs) further emphasize the urgent need for novel therapeutic strategies. In this context, natural killer cell-derived extracellular vesicles (NK-EVs) have emerged as a promising cell-free therapeutic approach that exhibits high tumor infiltration and cytotoxicity against cancer cells and CSCs.

This study aims to investigate the efficacy of NK-EVs as a therapeutic strategy for TNBC using various clinically relevant models, including patient-derived xenografts. Pathway analysis suggests strong activation of apoptosis via canonical caspase activation, as well as necrosis, thereby confirming the important cytotoxic effect of NK-EVs.

Interestingly, NK-EVs were also found to suppress TNBC CSCs by disrupting their functionality and viability, and NK-EV treatment increased the expression of apoptosis markers in both CSCs and non-CSCs. By elucidating the therapeutic efficacy and translational potential of NK-EV-based interventions in TNBC, these findings offer critical insights for the development of future immunotherapeutic strategies against this aggressive subtype of breast cancer.

论文信息

作者
Kirkby M、St-Denis-Bissonnette F、Diab MD、Mediratta K、Korobkow A、Humber J、Han P、Muradia G
单位
Biologic and Radiopharmaceutical Drugs Directorate, Health Canada, Ottawa, ON K1A 0K9, Canada.Canada
期刊
Nanomaterials (Basel, Switzerland)2026 Apr 27
原文标识
PubMed 42117942 · DOI 10.3390/nano16090525