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浸润性 NK 细胞在胶质母细胞瘤干样肿瘤球中结合、裂解并提高化疗疗效

英文原题:Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.

查看英文原题

Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.

PubMed 2022/05/10(内容时间) Commun Biol Q1 · IF 5.8(JCR 2025)

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中文摘要

胶质母细胞瘤仍然是最致命的原发性脑肿瘤。基于自然杀伤(NK)细胞的治疗是治疗胶质母细胞瘤的一种有前景的免疫治疗策略,因为这些细胞能够选择并裂解治疗耐药的胶质母细胞瘤干细胞样细胞(GSLCs)。使用超级NK细胞的免疫治疗具有作为抗肿瘤方法的潜力,因为我们发现其在2D和3D模型中杀伤患者来源的GSLCs的效率,可能逆转患者中也观察到的免疫抑制。除了其强大的细胞毒性外,NK细胞分泌IFN-,上调GSLC表面CD54和MHC I类分子的表达,并增加GSLCs对化疗药物的敏感性。此外,NK细胞在胶质母细胞瘤组织中血管周围区域的定位及其在肿瘤球中与GSLCs的密切接触表明其具有浸润胶质母细胞瘤肿瘤并靶向GSLCs的能力。由于GSLC在其分化阶段方面具有异质性和可塑性,应设计个性化免疫治疗策略以有效靶向胶质母细胞瘤。

展开英文摘要原文

Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients.

In addition to their potent cytotoxicity, NK cells secrete IFN- , upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs.

Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.

论文信息

作者
Breznik B、Ko MW、Tse C、Chen PC、Senjor E、Majc B、Habič A、Angelillis N
第一作者单位
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA. barbara.breznik@nib.si.United States
通讯作者单位
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA. AJewett@mednet.ucla.edu.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Communications biology2022 May 10
原文标识
PubMed 35538218 · DOI 10.1038/s42003-022-03402-z