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侵袭多形性胶质母细胞瘤的T淋巴细胞凋亡:一种可能的肿瘤防御机制。

Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism.

作者信息

Didenko Vladimir V, Ngo Hop N, Minchew Candace, Baskin David S

机构信息

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.

出版信息

J Neurosurg. 2002 Mar;96(3):580-4. doi: 10.3171/jns.2002.96.3.0580.

Abstract

OBJECT

The goal of this study was to investigate whether apoptosis occurs in T lymphocytes that invade Fas ligand (FasL)-expressing glioblastomas multiforme (GBMs) and if its induction could be mediated by Fas.

METHODS

Apoptotic T lymphocytes were detected in GBMs by using detection of cell-type markers combined with active caspase-3 immunohistochemical analysis, a recently introduced apoptosis-specific in situ ligation assay, as well as by examining morphological criteria. Apoptotic T cells expressed Fas and were localized in the vicinity or in direct contact with FasL-expressing tumor cells. The T lymphocytes were undergoing apoptosis in spite of Bcl-2 expression. Expression of Bax was also detected in dying T cells, which can explain the absence of the protective effect of Bcl-2. because Bax inhibits Bcl-2 death-repressor activity.

CONCLUSIONS

On the basis of the data presented in this paper, the authors suggest that GBM cells that express FasL can induce apoptosis in invading immune cells. This phenomenon may play an important role in these tumors' maintenance of immune privilege and evasion of immune attacks. Awareness of this phenomenon should be helpful for the development of novel strategies for treatment of malignant gliomas.

摘要

目的

本研究的目的是调查侵入表达Fas配体(FasL)的多形性胶质母细胞瘤(GBM)的T淋巴细胞中是否发生凋亡,以及其诱导是否可由Fas介导。

方法

通过使用细胞类型标志物检测结合活性半胱天冬酶-3免疫组织化学分析、最近引入的凋亡特异性原位连接测定法以及检查形态学标准,在GBM中检测凋亡T淋巴细胞。凋亡T细胞表达Fas,并定位在表达FasL的肿瘤细胞附近或与之直接接触。尽管有Bcl-2表达,T淋巴细胞仍在发生凋亡。在濒死T细胞中也检测到Bax的表达,这可以解释Bcl-2缺乏保护作用的原因,因为Bax抑制Bcl-2的死亡抑制活性。

结论

基于本文提供的数据,作者认为表达FasL的GBM细胞可诱导侵入的免疫细胞凋亡。这种现象可能在这些肿瘤维持免疫豁免和逃避免疫攻击中起重要作用。认识到这种现象应该有助于开发治疗恶性胶质瘤的新策略。

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