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胶质瘤肿瘤干细胞调控局部肿瘤免疫环境

英文原题:Glioma cancer stem cells modulating the local tumor immune environment.

查看英文原题

Glioma cancer stem cells modulating the local tumor immune environment.

PubMed 2022/10/10(内容时间) Front Mol Neurosci Q2 · IF 4.4(JCR 2025)

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中文摘要

胶质瘤干细胞(GSCs)驱动胶质瘤肿瘤的耐药机制,并介导对固有免疫和适应性免疫应答的抑制。在此,我们研究胶质瘤干细胞中间充质-上皮转化因子(c-Met)和Fas受体的表达,以及它们通过调节TIL(肿瘤浸润淋巴细胞)群体在增强肿瘤介导的免疫抑制中的作用。收集了4例接受胶质母细胞瘤手术患者的肿瘤组织。将GSCs作为神经球培养,并通过流式细胞术评估CD133、c-Met和FasL的共表达。分离TILs,并使用流式细胞术评估淋巴细胞亚群频率,包括CD3 +、CD4 +、CD8 +、调节性T细胞(FOXP3 + CD25)和小胶质细胞(CD11b + CD45)。

我们的研究结果显示,在全部四个样本中,相当一部分GSCs表达c-Met(89-99%)和FasL(73-97%)。在局部免疫细胞中发现小胶质细胞群体显著较低,范围为3%至5%。

我们未发现c-Met + GSC和FasL + GSC的表达与局部和全身免疫细胞之间存在统计学显著相关性。这可能与样本量较小有关。c-Met +和FasL + GSC群体的百分比似乎与胶质母细胞瘤患者中细胞毒性T细胞、调节性T细胞和小胶质细胞群体的百分比相关。有必要在更大样本量中进一步研究。

展开英文摘要原文

Glioma stem cells (GSCs) drive the resistance mechanism in glioma tumors and mediate the suppression of innate and adaptive immune responses.

Here we investigate the expression of mesenchymal-epithelial transition factor (c-Met) and Fas receptor in GSCs and their role in potentiating the tumor-mediated immune suppression through modulation of tumor infiltrating lymphocyte (TIL) population. Tumor tissues were collected from 4 patients who underwent surgery for glioblastoma.

GSCs were cultured as neurospheres and evaluated for the co-expression of CD133, c-Met and FasL through flow cytometry. TILs were isolated and evaluated for the lymphocyte subset frequencies including CD3 +, CD4 +, CD8 +, regulatory T cells (FOXP3 + CD25) and microglia (CD11b + CD45) using flow cytometry.

Our findings revealed that a significant population of GSCs in all four samples expressed c-Met (89-99%) and FasL (73-97%). A significantly low microglia population was found in local immune cells ranging from 3 to 5%.

We did not find a statistically significant correlation between expressions of c-Met + GSC and FasL + GSC with local and systemic immune cells. This may be regarded to the small sample size. The percent c-Met + and FasL + GSC population appeared to be related to percent cytotoxic T cells, regulatory T cells and microglia populations in glioblastoma patients.

Further investigation is warranted in a larger sample size.

论文信息

作者
Khan I、Mahfooz S、Karacam B、Elbasan EB、Akdur K、Karimi H、Sakarcan A、Hatiboglu MA
单位
Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkey.Turkey
期刊
Frontiers in molecular neuroscience2022
原文标识
PubMed 36299858 · DOI 10.3389/fnmol.2022.1029657