CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma.
Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma.
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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。
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.
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