Cellular immunity of patients with malignant glioma:: prerequisites for dendritic cell vaccination immunotherapy
Cellular immunity of patients with malignant glioma:: prerequisites for dendritic cell vaccination immunotherapy
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DOI：
10.3171/jns.2006.105.1.41
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发表时间：
2006-07-01
影响因子：
4.1
通讯作者：
Sorg, Rudiger V.
中科院分区：
文献类型：
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作者：
Rapp, Marion;Oezcan, Zakir;Sorg, Rudiger V.
目的。使用树突状细胞（DC）的疫苗接种疗法是一种有前途的免疫治疗方法。然而，它依赖于完整的细胞免疫和成熟 DC 的有效生成，这两者在神经胶质瘤患者中都可能受到损害。因此，对此类患者的免疫状态和体外DC生成进行了研究。方法。采用流式细胞术分析高级别胶质瘤患者和健康对照志愿者的白细胞亚群和单核细胞来源的成熟DC的频率。与对照组志愿者相比，患者中淋巴细胞、T细胞和B细胞的频率减少，而中性粒细胞和单核细胞的频率增加。两组之间的白细胞计数或 NK 细胞和主要 T 细胞亚群的频率没有差异。 T 细胞对凝集素刺激的反应正常。对于单核细胞，在患者中观察到 CD80(+) 和 CD86(+) 细胞频率较低，但 CD40(+) 和 HLA-DRI 细胞频率较低。在自体血浆补充培养基或无血清培养基中，通过两步培养方案进行的离体 DC 生成显示，患者组和对照组之间的 CD80(+) 和 HLA-DR 表达仅存在微小差异。 CD83(+)、CD1a(+)、CD14(-)、CD40(+)和CD86(+)细胞的频率相当。总体而言，无血清培养基优于补充血浆的培养基，并且可以有效地离体产生CD83(+)、CD1a(+)和CD14(-)成熟DC。结论。仅观察到神经胶质瘤患者的免疫状态存在轻微缺陷，这可能不会妨碍免疫治疗。可以从神经胶质瘤患者的单核细胞中成功大量产生具有典型免疫表型的成熟树突状细胞，特别是在无血清条件下。
Object. Vaccination therapy that uses dendritic cells (DCs) is a promising immunotherapeutic approach. However, it relies on intact cellular immunity and efficient generation of mature DCs, both of which can be impaired in patients with glioma. Therefore, the immune status and ex vivo generation of DC in such patients were studied.Methods. The frequencies of white blood cell subsets and monocyte-derived, mature DCs in patients with high-grade gliomas and healthy control volunteers were analyzed using flow cytometry.In the patients, frequencies of lymphocytes, T cells, and B cells were reduced in comparison with the volunteers in the control group, whereas frequencies of neutrophils and monocytes were increased. There were no differences between the two groups in terms of white blood cell counts or the frequency of NK cells and the major T-cell subsets. The responsiveness of T cells to lectin stimulation was normal. For monocytes, lower frequencies of CD80(+) and CD86(+) cells but not of CD40(+) and HLA-DRI cells were observed in patients. Ex vivo DC generation in a two-step culture protocol in autologous plasma-supplemented medium or in serum-free medium showed only minor differences in CD80(+) and HLA-DR expression between the patient and control groups. Frequencies of CD83(+), CD1a(+), CD14(-), CD40(+), and CD86(+) cells were comparable. Overall, the serum-free medium was superior to the plasma-supplemented medium and allowed efficient ex vivo generation of CD83(+), CD1a(+), and CD14(-) mature DCs.Conclusions. Only minor defects in the immune status of patients with glioma were observed, which probably would not hamper immunotherapy. Mature DCs can be generated successfully in nonnal numbers and with typical immunophenotypes from monocytes of patients with glioma, particularly under serum-free conditions.