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首页> 外文期刊>Neurosurgery >Systematic Comparison of Dendritic Cell-based Immunotherapeutic Strategies for Malignant Gliomas: In Vitro Induction of Cytolytic and Natural Killer-like T Cells.
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Systematic Comparison of Dendritic Cell-based Immunotherapeutic Strategies for Malignant Gliomas: In Vitro Induction of Cytolytic and Natural Killer-like T Cells.

机译:恶性胶质瘤基于树突状细胞的免疫治疗策略的系统比较:胞浆和自然杀伤性T细胞的体外诱导。

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摘要

OBJECTIVE: To compare the efficacy of various immunotherapeutic strategies of loading dendritic cells (DCs) with whole-glioma cell antigens and characterize the effector responses induced. METHODS: DCs were either fused with major histocompatibility complex (MHC)-matched glioma cells (Fusion) or pulsed with apoptotic tumor cells (DC/Apo), total tumor ribonucleic acid (RNA) (DC/RNA), or tumor lysate (DC/Lys). These tumor-DC preparations were then assessed for their phenotype, cytokine profile, and capacity to stimulate autologous peripheral blood mononuclear cells (PBMCs) in vitro. Phenotype and tumor-specific cytolytic activities of various effector cell populations were characterized and compared. RESULTS: The various tumor-DC preparations exhibited similar phenotype and cytokine profiles irrespective of the method of loading tumor-cell antigens. However, the fusion, DC/Apo, and DC/RNA induced superior tumor cytolytic activities in PBMCs compared with DC/Lys or DC and tumor controls. DC/Apo induced the greatest expansion of tumor-specific lymphocytes, as detected by trypan blue exclusion and thymidine incorporation assays. Flow cytometric analyses also revealed the highest relative percentages of T helper cells (CD3(+)CD4(+)), cytotoxic T lymphocytes (CTLs) (CD3(+)CD8(+)), and natural killer (NK)-like T cells (CD3(+)CD56(+)) in the DC/Apo group among all the groups studied, indicating that DC/Apo induced expansion of PBMCs bearing multiple T and NK cell markers. Interestingly, isolated NK-like T cells demonstrated significantly higher tumor cytotoxicity compared with CTLs isolated from the same groups and was also non-MHC-restricted. CONCLUSION: Apoptotic tumor cells may be an optimal source of whole-tumor-cell antigen for immunotherapy of gliomas. The study also demonstrates for the first time that both CTLs and NK-like T cells are expanded and stimulated by mature, tumor-pulsed DCs.
机译:目的:比较负载树突状细胞(DC)和整个神经胶质瘤细胞抗原的各种免疫治疗策略的疗效,并表征诱导的效应反应。方法:将DC与主要组织相容性复合物(MHC)匹配的神经胶质瘤细胞(融合)融合,或与凋亡性肿瘤细胞(DC / Apo),总肿瘤核糖核酸(RNA)(DC / RNA)或肿瘤裂解液(DC)融合。 / Lys)。然后评估这些肿瘤DC制剂的表型,细胞因子谱以及体外刺激自体外周血单个核细胞(PBMC)的能力。表征和比较了各种效应细胞群体的表型和肿瘤特异性溶细胞活性。结果:各种肿瘤-DC制剂表现出相似的表型和细胞因子谱,而与加载肿瘤细胞抗原的方法无关。但是,与DC / Lys或DC和肿瘤对照相比,融合,DC / Apo和DC / RNA在PBMC中诱导了优异的肿瘤细胞溶解活性。通过台盼蓝排除法和胸苷掺入法检测,DC / Apo诱导了肿瘤特异性淋巴细胞的最大扩增。流式细胞仪分析还揭示了T辅助细胞(CD3(+)CD4(+)),细胞毒性T淋巴细胞(CTL)(CD3(+)CD8(+))和自然杀伤性(NK)样T的相对百分比最高在所有研究的组中,DC / Apo组中的CD3(+)CD56(+)细胞(CD3(+)CD56(+)),表明DC / Apo诱导了带有多个T和NK细胞标记物的PBMC扩增。有趣的是,与从相同组分离的CTL相比,分离的NK样T细胞表现出明显更高的肿瘤细胞毒性,并且不受MHC限制。结论:凋亡的肿瘤细胞可能是胶质瘤免疫治疗的全肿瘤细胞抗原的最佳来源。这项研究还首次证明,成熟的,受肿瘤脉冲的DC可以扩展CTL和NK样T细胞。

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