Human Glioblastoma Stem-Like Cells are More Sensitive to Allogeneic NK and T Cell-Mediated Killing Compared with Serum-Cultured Glioblastoma Cells
Human Glioblastoma Stem-Like Cells are More Sensitive to Allogeneic NK and T Cell-Mediated Killing Compared with Serum-Cultured Glioblastoma Cells
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DOI：
10.1111/j.1750-3639.2011.00515.x
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发表时间：
2012-03-01
期刊：
影响因子：
6.4
通讯作者：
Quillien, Veronique
中科院分区：
文献类型：
--
作者：
Avril, Tony;Vauleon, Elodie;Quillien, Veronique
多形性胶质母细胞瘤（GBM）是最严重的原发性脑癌，由于疾病不可避免的复发，预后很差。诊断后的中位总生存期小于1年。最近在GBM中发现了肿瘤干细胞。GBM干细胞样细胞（GSCs）表现出对放射/化疗治疗的抗性，因此被认为在疾病复发中起重要作用。因此，GSCs是GBM患者新疗法的有吸引力的靶点。在这项研究中，我们发现，由于MHC I类分子的表达，具有干细胞特征的GBM细胞对静止自然杀伤（NK）细胞介导的裂解具有抗性。然而，GSCs被凝集素激活的NK细胞杀死。此外，在使用治疗性抗体西妥昔单抗的实验中，我们发现GSCs对抗体介导的细胞毒性敏感。我们证实了GSC对il - 2激活的NK细胞和肿瘤特异性T细胞进行的细胞毒性的敏感性。更重要的是，我们发现相对于从相同的初始肿瘤标本中获得的相应血清培养的GBM细胞，GSCs对NK和T细胞介导的裂解更敏感。总之，这些结果证明了GSC对免疫细胞毒性的敏感性，因此强烈提示GSC是GBM患者免疫治疗的合适靶细胞。
Glioblastoma multiforme (GBM) is the most dramatic primary brain cancer with a very poor prognosis because of inevitable disease recurrence. The median overall survival is less than 1 year after diagnosis. Cancer stem cells have recently been disclosed in GBM. GBM stem-like cells (GSCs) exhibit resistance to radio/chemotherapeutic treatments and are therefore considered to play an important role in disease recurrence. GSCs are thus appealing targets for new treatments for GBM patients. In this study, we show that GBM cells with stem cell characteristics are resistant to lysis mediated by resting natural killer (NK) cells because of the expression of MHC class I molecules. However, GSCs are killed by lectin-activated NK cells. Furthermore, in experiments using the therapeutic antibody CetuximAb, we show that GSCs are sensitive to antibody-mediated cytotoxicity. We confirm the sensitivity of GSC to cytotoxicity carried out by IL2-activated NK cells and tumor-specific T cells. More importantly, we show that GSCs are more sensitive to NK and T cell-mediated lysis relatively to their corresponding serum-cultured GBM cells obtained from the same initial tumor specimen. Altogether, these results demonstrate the sensitivity of GSC to immune cell cytotoxicity and, therefore, strongly suggest that GSCs are suitable target cells for immunotherapy of GBM patients.