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PTPN7 mediates macrophage‐polarization and determines immunotherapy in gliomas: A single‐cell sequencing analysis
Environmental Toxicology ( IF 4.5 ) Pub Date : 2024-04-06 , DOI: 10.1002/tox.24259
Xiang Ji 1 , Jingsong Cheng 1 , Jing Su 1 , Rong Wen 1 , Qi Zhang 2 , Guodong Liu 1 , Yun Peng 3, 4 , Jinning Mao 5
Affiliation  

BackgroundProtein tyrosine phosphatase non‐receptor type 7 (PTPN7) is a signaling molecule that regulates a multitude of cellular processes, spanning cell proliferation, cellular differentiation, the mitotic cycle, and oncogenic metamorphosis. However, the characteristic of PTPN7 in the glioma microenvironment has yet to be elucidated.MethodsThe prognostic value, genomic features, immune characteristics, chemotherapy prediction, and immunotherapy prediction of PTPN7 were systematically explored at the bulk sequencing level. The cell evolution trajectory, cell communication pattern, and cell metabolic activity related to PTPN7 were systematically explored at the single‐cell sequencing level. HMC3 and M0 cells were cocultured with U251 and T98G cells, and flow cytometry was carried out to investigate the polarization of HMC3 and M0. Transwell assay and CCK‐8 assay were performed to explore the migration and proliferation activity of U251 and T98G.ResultsThe expression level of PTPN7 is significantly elevated in glioma and indicates malignant features. PTPN7 expression predicts worse prognosis of glioma patients. PTPN7 is associated with genome alteration and immune infiltration. Besides, PTPN7 plays a crucial role in modulating metabolic and immunogenic processes, particularly by influencing the activity of microglia and macrophages through multiple signaling pathways involved in cellular communication. Specifically, PTPN7 actively mediates inflammation‐resolving‐polarization of macrophages and microglia and protects glioma from immune attack. PTPN7 could also predict the response of immunotherapy.ConclusionsPTPN7 is critically involved in inflammation‐resolving‐polarization mediated by macrophage and microglia and promotes the immune escape of glioma cells.

中文翻译:

PTPN7 介导巨噬细胞极化并决定神经胶质瘤的免疫治疗:单细胞测序分析

背景蛋白酪氨酸磷酸酶非受体 7 型 (PTPN7) 是一种信号分子,可调节多种细胞过程,包括细胞增殖、细胞分化、有丝分裂周期和致癌变态。然而,PTPN7在胶质瘤微环境中的特性尚未阐明。方法在批量测序水平上系统探讨PTPN7的预后价值、基因组特征、免疫特征、化疗预测和免疫治疗预测。在单细胞测序水平上系统地探讨了与PTPN7相关的细胞进化轨迹、细胞通讯模式和细胞代谢活动。 HMC3和M0细胞与U251和T98G细胞共培养,并进行流式细胞术研究HMC3和M0的极化。采用Transwell实验和CCK-8实验探讨U251和T98G的迁移和增殖活性。结果PTPN7在胶质瘤中表达水平显着升高,提示胶质瘤的恶性特征。 PTPN7 表达预示神经胶质瘤患者预后较差。 PTPN7 与基因组改变和免疫浸润相关。此外,PTPN7 在调节代谢和免疫原性过程中发挥着至关重要的作用,特别是通过参与细胞通讯的多种信号通路影响小胶质细胞和巨噬细胞的活性。具体来说,PTPN7 主动介导巨噬细胞和小胶质细胞的炎症消解极化,并保护神经胶质瘤免受免疫攻击。 PTPN7还可以预测免疫治疗的反应。结论PTPN7关键参与巨噬细胞和小胶质细胞介导的炎症消解极化,并促进胶质瘤细胞的免疫逃逸。
更新日期:2024-04-06
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