NK Cells Recognize and Kill Human Glioblastoma Cells with Stem Cell-Like Properties

NK Cells Recognize and Kill Human Glioblastoma Cells with Stem Cell-Like Properties
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DOI:
10.4049/jimmunol.0802845
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发表时间:
2009-03-15
影响因子:
4.4
通讯作者:
Bottino, Cristina
Bottino, Cristina
中科院分区:
医学2区
文献类型:
--
作者:
Castriconi, Roberta;Daga, Antonio;Bottino, Cristina

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在这项研究中,癌细胞是从9个胶质母细胞瘤患者的肿瘤标本中分离出来的。胶质母细胞瘤细胞,在合适的培养条件下培养,显示典型的神经干细胞的标志物,能够在体外部分多系分化,并给予起源时,原位注射在NOD/SCID小鼠浸润性肿瘤。这些细胞虽然对新鲜分离的NK细胞具有抗性,但对同种异体和自体IL-2(或IL-15)激活的NK细胞介导的裂解高度敏感。事实上,分析的所有干细胞培养的胶质母细胞瘤细胞都不表达保护量的HILA I类分子,而表达触发最佳NK细胞细胞毒性的活化NK受体的各种配体。重要的是,胶质母细胞瘤干细胞表达高水平的PVR和Nectin-2,DNAM-1激活NK受体的配体。免疫学杂志,2009,182:3530-3539.
In this study, cancer cells were isolated from tumor specimens of nine glioblastoma patients. Glioblastoma cells, cultured under suitable culture conditions, displayed markers typical of neural stem cells, were capable of partial multilineage differentiation in vitro, and gave origin to infiltrating tumors when orthotopically injected in NOD/SCID mice. These cells, although resistant to freshly isolated NK cells, were highly susceptible to lysis mediated by both allogeneic and autologous IL-2 (or IL-15)-activated NK cells. Indeed, all stem cell-cultured glioblastoma cells analyzed did not express protective amounts of HILA class I molecules, while expressing various ligands of activating NK receptors that triggered optimal NK cell cytotoxicity. Importantly, glioblastoma stem cells expressed high levels of PVR and Nectin-2, the ligands of DNAM-1-activating NK receptor. The Journal of Immunology, 2009,182: 3530-3539.