Characterization and immunotherapeutic potential of γδ T-cells in patients with glioblastoma
Characterization and immunotherapeutic potential of γδ T-cells in patients with glioblastoma
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DOI：
10.1215/15228517-2008-111
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发表时间：
2009-08-01
期刊：
影响因子：
15.9
通讯作者：
Lamb, Lawrence S., Jr.
中科院分区：
文献类型：
--
作者：
Bryant, Nichole L.;Suarez-Cuervo, Catalina;Lamb, Lawrence S., Jr.
多形性胶质母细胞瘤（GBM）的经典免疫学方法显示出混合的结果，并且专注于针对GBM的先天淋巴细胞活性的疗法尚未得到严格评估。我们在GBM治疗前和治疗期间的选定时间点检查了外周血淋巴细胞表型、γ δ T细胞数量、促有丝分裂反应和对GBM细胞系和GBM患者原发性肿瘤外植体的细胞毒性。健康志愿者作为对照，并按年龄分组。通过CD 3和T细胞受体γ δ染色评估这些患者肿瘤的T细胞浸润。我们的研究结果显示，在GBM切除前和切除后即刻，健康志愿者和患者的平均绝对T细胞计数、T细胞亚群CD 3（+）CD 4（+）和CD 3（+）CD 8（+）以及自然杀伤细胞计数没有差异。相比之下，γ δ T细胞计数和γ δ T细胞的有丝分裂原刺激的增殖反应在GBM切除前和整个治疗过程中显著降低。来自患者和健康志愿者的扩增/活化的γ δ T细胞杀死GBM细胞系D54、U373和U251以及原代GBM，而对原代星形胶质细胞培养物没有细胞毒性。在石蜡切片中观察到血管周围T细胞积聚，但未观察到有组织的T细胞侵入肿瘤实质。综合起来，这些数据表明.. T细胞耗竭和功能受损发生在肿瘤生长之前或同时。来自健康对照和所选患者的扩增/活化的γ δ T细胞对原代GBM外植体的显著细胞毒性可能开启了先前未探索的GBM细胞免疫治疗方法。Neuro-Oncology 11，357 - 367，2009（Posted to Neuro-Oncology [serial online]，Doc. D 08 -00113，2009年2月11日。网址http://neuro-oncology.dukejournals.org; DOI：10.1215/15228517-2008-111）
Classical immunotherapeutic approaches to glioblastoma multiforme (GBM) have shown mixed results, and therapies focused on innate lymphocyte activity against GBM have not been rigorously evaluated. We examined peripheral blood lymphocyte phenotype, gamma delta T-cell number, mitogenic response, and cytotoxicity against GBM cell lines and primary tumor explants from GBM patients at selected time points prior to and during GBM therapy. Healthy volunteers served as controls and were grouped by age. T-cell infiltration of tumors from these patients was assessed by staining for CD3 and T-cell receptor gamma delta. Our findings revealed no differences in counts of mean absolute T-cells, T-cell subsets CD3(+)CD4(+) and CD3(+)CD8(+), and natural killer cells from healthy volunteers and patients prior to and immediately after GBM resection. In contrast, gamma delta T-cell counts and mitogen-stimulated proliferative response of gamma delta T-cells were markedly decreased prior to GBM resection and throughout therapy. Expanded/activated gamma delta T-cells from both patients and healthy volunteers kill GBM cell lines D54, U373, and U251, as well as primary GBM, without cytotoxicity to primary astrocyte cultures. Perivascular T-cell accumulation was noted in paraffin sections, but no organized T-cell invasion of the tumor parenchyma was seen. Taken together, these data suggest that.. T-cell depletion and impaired function occur prior to or concurrent with the growth of the tumor. The significant cytotoxicity of expanded/activated gamma delta T-cells from both healthy controls and selected patients against primary GBM explants may open a previously unexplored approach to cellular immunotherapy of GBM. Neuro-Oncology 11, 357 - 367, 2009 ( Posted to Neuro-Oncology [serial online], Doc. D08-00113, February 11, 2009. URL http://neuro-oncology.dukejournals.org; DOI:10.1215/15228517-2008-111)