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减毒新城疫病毒 (NDV) 激活的 NK 细胞作为抗癌治疗

英文原题:Natural killer cell activated by attenuated newcastle disease virus (NDV) as anti-cancer therapy.

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Natural killer cell activated by attenuated newcastle disease virus (NDV) as anti-cancer therapy.

PubMed 2026/03/19(内容时间) Front Mol Biosci Q2 · IF 4.4(JCR 2025)

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研究概要

减毒 NDV 显著增强 NK 细胞对乳腺癌细胞的细胞毒性和黏附作用。这种联合策略提供了一种有前景的免疫治疗策略,凸显了将溶瘤病毒治疗与基于 NK 细胞的治疗相结合用于癌症治疗的潜力。

研究思路结论见上方概要

自然杀伤(NK)细胞在先天免疫中发挥核心作用,能够无需预先致敏即靶向病毒感染细胞和恶性细胞。然而,其活性在肿瘤微环境中常受到抑制。溶瘤病毒如新城疫病毒(NDV)不仅选择性在肿瘤细胞中复制,还能刺激免疫反应,尤其是NK细胞活化。因此,将减毒NDV与NK细胞疗法联合可能增强抗肿瘤疗效。

本研究旨在探讨减毒NDV激活的NK细胞对乳腺癌细胞系AMJ13和MCF-7的协同抗癌潜力,重点关注细胞毒性、黏附和免疫表型变化。

采用分离培养基和8 m滤网过滤从外周血中分离NK细胞,随后在含interleukin-15(IL-15)的培养基中扩增。通过免疫荧光检测CD3、CD16、Cd56和CD57表达,对NK细胞进行免疫表型鉴定。将AMJ13和MCF-7细胞暴露于NK细胞、NDV或二者联合后,采用WST法评估共细胞毒性。通过光学显微镜、扫描电子显微镜(SEM)和CD56免疫荧光检测评估NK细胞与肿瘤细胞的黏附。使用GraphPad Prism进行统计分析,并使用CompuSyn软件分析联合效应。

NK 细胞在添加 IL-15 的培养中有效扩增,并与 NDV 联合时表现出增强的细胞毒性,导致 AMJ13 和 MCF-7 细胞的活力较单一处理显著降低(p < 0.05)。光学和 SEM 分析显示 NK 细胞黏附、形态改变以及肿瘤细胞表面破坏。免疫荧光证实处理组中 NK 标志物(CD56)组合表达增加,支持 NK 细胞功能性增强附着。

展开英文摘要原文

Natural Killer (NK) cells play a central role in innate immunity by targeting virally infected and malignant cells without prior sensitization. However, their activity is often suppressed within the tumor microenvironment. Oncolytic viruses such as Newcastle Disease Virus (NDV) not only selectively replicate in tumor cells but also stimulate immune responses, particularly NK cell activation. Combining attenuated NDV with NK cell therapy may therefore enhance anti-tumor efficacy. AIM: This study aimed to investigate the synergistic anti-cancer potential of NK cells activated by attenuated NDV against breast cancer cell lines AMJ13 and MCF-7, with emphasis on cytotoxicity, adhesion, and immunophenotypic changes.

NK cells were isolated from peripheral blood using separation media and 8 m mesh filtration, followed by expansion in culture with interleukin-15 (IL-15). Immunofluorescence assays were performed to characterize these NK cells by immunophenotyping through detection of CD3, CD16, Cd56 and CD57 expressions. Co-cytotoxicity was evaluated by WST assay in AMJ13 and MCF-7 cells exposed to NK cells, NDV, or the combination. NK adhesion to tumor cells was assessed by light microscope, scanning electron microscopy (SEM) and immunofluorescence by CD56 detection. Statistical analysis was conducted using GraphPad Prism, and combination effects were analyzed by CompuSyn software.

NK cells expanded effectively in IL-15-supplemented culture and displayed enhanced cytotoxicity when combined with NDV, leading to significantly reduced viability in both AMJ13 and MCF-7 cells compared with single treatments (p < 0.05). light and SEM analyses demonstrated NK cell adhesion, morphological alterations, and surface disruption of tumor cells. Immunofluorescence confirmed increased expression of NK marker (CD56) combination in treated groups, supporting functional enhance attachemtn of NK cells.

Attenuated NDV significantly augments NK cell-mediated cytotoxicity and adhesion against breast cancer cells. This combinatorial approach offers a promising immunotherapeutic strategy, highlighting the potential of integrating oncolytic virotherapy with NK cell-based therapy for cancer treatment.

论文信息

作者
Al-Hayani NN、Salman MI、Al-Shammari AM
第一作者单位
College of Medicine, University of Anbar, Ramadi, Iraq.
通讯作者单位
Experimental Therapy, Iraqi Center for Cancer and Medical Genetics Research, Mustansiriyah University, Baghdad, Iraq.
期刊
Frontiers in molecular biosciences2026
原文标识
PubMed 41938014 · DOI 10.3389/fmolb.2026.1721060