nature-medicine201212-9

俄亥俄州立大学的研究人员发现,癌症患者会对抗癌性病毒的感染产生响应。在病毒感染大脑癌细胞后的数小时内,一种名为自然杀伤细胞的特殊免疫细胞会移动到大脑并去除大脑中的治疗性病毒。

-2012年12月《自然-医学》


中文翻译


【题目】NK细胞识别NKp30和NKp46天然细胞毒性受体,阻碍成胶质细胞瘤的病毒疗法

【译文】成胶质瘤细胞在对溶瘤细胞单纯疱疹病毒(oHSV)治疗的免疫反应中的作用存在争论,因为它可能增强或抑制功效。我们发现小鼠成胶质细胞瘤oHSV感染的数小时内,激活的自然杀伤(NK)细胞被招募至感染位点。该反应大幅削弱了成胶质细胞瘤病毒治疗的功效。oHSV活化的NK细胞协同肿瘤内巨噬细胞和小神经胶质的活化。在体外,人NK细胞优先溶解oHSV感染的人成胶质细胞瘤细胞系。这增强了依赖NK细胞自然细胞毒性受体(NCRs) NKp30和NKp46的杀伤作用,这些受体的配体在oHSV感染的成胶质细胞瘤中上调。我们发现HSV效价和oHSV效能在Ncr1−/− 小鼠和神经胶质瘤Ncr1−/− NK细胞继承性转移模型中分别增加。这些结果证实了成胶质细胞瘤病毒治疗受到一种参与特异性NCR的抗病毒NK细胞反应的部分限制,发现了增强癌症病毒治疗的新潜在靶点。

英文原稿


[Title]: NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors

[Authors]:Christopher A Alvarez-Breckenridge,1, 2, 10 Jianhua Yu,3, 4, 10 Richard Price,1, 2 Jeffrey Wojton,2 Jason Pradarelli,2 Hsiaoyin Mao,4 Min Wei,4 Yan Wang,2 Shun He,4 Jayson Hardcastle,2 Soledad A Fernandez,4, 5 Balveen Kaur,2, 4 Sean E Lawler,2 Eric Vivier,6 Ofer Mandelboim,7 Alessandro Moretta,8 Michael A Caligiuri3, 4 & E Antonio Chiocca2, 4, 9

[Abstract]The role of the immune response to oncolytic Herpes simplex viral (oHSV) therapy for glioblastoma is controversial because it might enhance or inhibit efficacy. We found that within hours of oHSV infection of glioblastomas in mice, activated natural killer (NK) cells are recruited to the site of infection. This response substantially diminished the efficacy of glioblastoma virotherapy. oHSV-activated NK cells coordinated macrophage and microglia activation within tumors. In vitro, human NK cells preferentially lysed oHSV-infected human glioblastoma cell lines. This enhanced killing depended on the NK cell natural cytotoxicity receptors (NCRs) NKp30 and NKp46, whose ligands are upregulated in oHSV-infected glioblastoma cells. We found that HSV titers and oHSV efficacy are increased in Ncr1−/− mice and a Ncr1−/− NK cell adoptive transfer model of glioma, respectively. These results demonstrate that glioblastoma virotherapy is limited partially by an antiviral NK cell response involving specific NCRs, uncovering new potential targets to enhance cancer virotherapy.

原文地址

http://www.nature.com/nm/journal/v18/n12/abs/nm.3013.html

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