研究动态
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GSDMA 处于神经胶质瘤焦亡和肿瘤免疫逃避的十字路口。

GSDMA at the crossroads between pyroptosis and tumor immune evasion in glioma.

发表日期:2023 Oct 28
作者: Ruicheng Zhang, Qiuya Song, Xiaoqian Lin, Bo Du, Deqin Geng, Dianshuai Gao
来源: Cell Death & Disease

摘要:

细胞焦亡是一种炎症性和程序性细胞死亡过程,其在肿瘤免疫中的作用一直存在争议。然而,作为gasdermin家族中的第一个分子,GSDMA在神经胶质瘤生长中的机制尚不清楚。我们利用TCGA数据库从Treg细胞相关基因中鉴定出差异表达基因GSDMA。使用开源数据库和平台研究了 GSDMA 的生物学功能以及 GSDMA 表达与肿瘤免疫细胞浸润和癌症患者生存之间的关系。此外,还使用流式细胞术分析检查 GSDMA 对肿瘤免疫细胞浸润的影响。我们的研究表明 GSDMA 表达在神经胶质瘤的免疫逃避中发挥重要作用。 GSDMA 高表达的患者预后较差。体内研究表明,GSDMA 敲低可以增强 CD8 T 细胞的浸润水平。高 GSDMA 表达还与 GBM 患者的抗 PD-L1 治疗效果不佳呈正相关,这表明 GSDMA 可能是一种潜在的生物标志物,应考虑与胶质瘤患者的抗 PD-L1 治疗联合使用。总之,我们的研究表明,神经胶质瘤中的高 GSDMA 表达与免疫浸润细胞 CD8 T 细胞和 Treg 细胞相关,并表明神经胶质瘤的预后较差。因此,GSDMA可能作为神经胶质瘤进展的治疗靶点,并应应用于神经胶质瘤患者的免疫治疗。版权所有©2023 Elsevier Inc.保留所有权利。
Pyroptosis, an inflammatory and programmed cell death process, has been controversial in its role in tumor immunity. However, as the first molecule in the gasdermin family, the mechanism of GSDMA in glioma growth is not well understood. We identified the differentially expressed gene GSDMA from Treg cells-related genes using the TCGA database. The biological functions of GSDMA and the relationship between GSDMA expression and tumor immune cell infiltration and cancer patient survival were investigated using open-source databases and platforms. Additionally, flow cytometry analysis was used to examine the effect of GSDMA on tumor immune cell infiltration. Our study showed that GSDMA expression played an important role in immune evasion in glioma. Patients with high GSDMA expression had a worse prognosis. In vivo studies demonstrated that GSDMA knockdown could enhance the infiltration level of CD8+ T cells. High GSDMA expression was also positively correlated with poor anti-PD-L1 treatment outcomes in GBM patients, suggesting that GSDMA may be a potential biomarker that should be considered in combination with anti-PD-L1 therapy for glioma patients. In conclusion, our study demonstrates that high GSDMA expression in gliomas is associated with immune-infiltrating cells CD8+ T cells and Treg cells, and indicates a worse prognosis in glioma. Therefore, GSDMA may serve as a therapeutic target for glioma progression and should be applied in immunotherapy for glioma patients.Copyright © 2023 Elsevier Inc. All rights reserved.