Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism
Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism
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DOI：
10.3171/jns.2002.96.3.0580
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发表时间：
2002-03-01
影响因子：
4.1
通讯作者：
Baskin, DS
中科院分区：
文献类型：
--
作者：
Didenko, VV;Ngo, HN;Baskin, DS
物体。本研究的目的是探讨侵袭Fas配体(FasL)表达的多形性胶质母细胞瘤(GBMs)的T淋巴细胞是否发生凋亡，以及FasL是否能介导其诱导凋亡。通过检测细胞类型标记物，结合活性caspase-3免疫组织化学分析，最近引入的一种凋亡特异性原位连接试验，以及通过检查形态标准，在GBM中检测到了凋亡的T淋巴细胞。凋亡T细胞表达Fas，定位于表达FasL的肿瘤细胞附近或直接接触。尽管有Bcl2的表达，但T淋巴细胞仍处于凋亡状态。在垂死的T细胞中也检测到Bax的表达，这可以解释为什么Bax抑制了Bcl2的死亡抑制活性，从而使Bcl2的保护作用消失。根据本文提供的数据，作者认为表达FasL的GBM细胞可以诱导侵袭性免疫细胞的凋亡。这一现象可能起到重要作用。在这些肿瘤维持免疫豁免权和逃避免疫攻击。对这一现象的认识应该有助于开发治疗恶性胶质瘤的新策略。
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.