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DC-CIK 细胞作为治疗胶质母细胞瘤潜在有效免疫治疗模型的临床前评估

英文原题:Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma.

查看英文原题

Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma.

PubMed 2025/01/03(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

尽管免疫疗法在多种癌症中具有良好效果,但其在中枢神经系统恶性肿瘤中的完全成功仍具挑战性。最近,一项针对胶质母细胞瘤(GBM)患者的细胞因子诱导杀伤(CIK)细胞免疫疗法的成功临床试验,为中枢神经系统恶性肿瘤的过继性细胞免疫疗法开辟了新途径。受这些发现的启发,我们在此研究了树突状细胞(DC)联合细胞因子诱导杀伤细胞(DC-CIK)是否也能提供一种替代且更有效的方式来提高GBM治疗的疗效。分析显示,DC-CIK细胞对胶质母细胞瘤细胞系表现出显著的细胞毒性作用,尤其是对具有干细胞样表型(GSCs)的细胞。

此外,通过共聚焦荧光显微镜证实,DC-CIK共培养后对这些细胞的特异性裂解增加。在GBM类器官(GBOs)中,发现肿瘤与效应细胞之间的直接相互作用高度有效。

此外,作为DC-CIK细胞针对GBM细胞模型的靶向机制,观察到细胞凋亡显著增加以及IFN-γ(而非TNF-α)分泌水平升高。

总体而言,我们提供了重要的初步证据,表明DC-CIK细胞可能在中枢神经系统恶性肿瘤,特别是胶质母细胞瘤的治疗中具有潜力。

展开英文摘要原文

Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies.

Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment. The analysis showed that DC-CIK cells exerted a significant cytotoxic effect on the glioblastoma cell lines, especially with the phenotype of stem-like cells (GSCs).

In addition, the increased specific lysis of these cells subsequent to DC-CIK co-culture was confirmed with confocal fluorescence microscope. The direct interactions between tumor and effector cells were found to be highly effective in GBM organoids (GBOs).

Moreover, a significant increase in apoptosis and elevated levels of IFN-γ (and not TNF-α) secretion were observed as a targeting mechanism of DC-CIK cells against GBM cell models.

Overall, we provide important preliminary evidence that DC-CIK cells may have potential in the treatment of CNS malignancies, particularly glioblastoma.

论文信息

作者
Lück AS、Pu J、Melhem A、Schneider M、Sharma A、Schmidt-Wolf IGH、Maciaczyk J
第一作者单位
Department of Stereotactic and Functional Neurosurgery, University Hospital of Bonn, 53127, Bonn, Germany.Germany
通讯作者单位
Department of Stereotactic and Functional Neurosurgery, University Hospital of Bonn, 53127, Bonn, Germany. jaroslaw.maciaczyk@ukbonn.de.Germany
文献类型
非美国政府资助研究
期刊
Scientific reports2025 Jan 3
原文标识
PubMed 39753685 · DOI 10.1038/s41598-024-84284-5