1. Academic Validation
  2. GSDMA at the crossroads between pyroptosis and tumor immune evasion in glioma

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

  • Biochem Biophys Res Commun. 2023 Oct 28:686:149181. doi: 10.1016/j.bbrc.2023.149181.
Ruicheng Zhang 1 Qiuya Song 2 Xiaoqian Lin 3 Bo Du 1 Deqin Geng 4 Dianshuai Gao 5
Affiliations

Affiliations

  • 1 Nanjing Medical University, Nanjing, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 2 Department of Pathology, Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 4 Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: gengdeqin@hotmail.com.
  • 5 Nanjing Medical University, Nanjing, China; Department of Human Anatomy and Neurobiology, Xuzhou Medical University, Xuzhou, China. Electronic address: gds@xzhmu.edu.cn.
Abstract

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.

Keywords

GSDMA; Glioma; Immune evasion; Pyroptosis.

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