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小胶质细胞与神经干细胞之间的串扰影响胶质母细胞瘤在 GBM 免疫微环境中的复发。

Crosstalk between microglia and neural stem cells influences the relapse of glioblastoma in GBM immunological microenvironment.

机构信息

Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.

Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China.

出版信息

Clin Immunol. 2023 Jun;251:109333. doi: 10.1016/j.clim.2023.109333. Epub 2023 Apr 23.

Abstract

Interactions between immunocytes and Neural Stem Cells (NSCs) in glioblastoma multiforme still remains unclear. Here, microglial cells and NSCs in peri-tumoral tissue were analyzed via single-cell whole-transcriptome sequencing. Results showed that two clusters of putative NSCs (the EGFRBCAN cell cluster, and the FABPTH19 cell cluster) exhibited immune-related functions. Two clusters of putative microglia (the XISTPDK4 and APOC1CCL3 cell clusters) exhibited the function of glial cell activation. The results of ligand receptor network analysis disclosed significant interactions between the APOC1CCL3 microglia and the NSCs. Correlation analysis on the overall survival (OS) and relapse-free survival (RFS) with 102 potential molecular targets in the TCGA database showed that a much larger number of molecules were correlated with RFS than with OS (34.31% vs. 8.82%), nine of them were validated in clinical specimens. In conclusion, crosstalk between APOC1CCL3 microglia and multiple molecule-labeled NSCs distal to the tumor core play certain roles on the recurrence of GBM.

摘要

胶质母细胞瘤中免疫细胞与神经干细胞(NSCs)之间的相互作用仍不清楚。本研究通过单细胞全转录组测序分析了肿瘤周围组织中的小胶质细胞和 NSCs。结果表明,两个潜在 NSCs 簇(EGFRBCAN 细胞簇和 FABPTH19 细胞簇)表现出与免疫相关的功能。两个潜在小胶质细胞簇(XISTPDK4 和 APOC1CCL3 细胞簇)表现出胶质细胞激活的功能。配体受体网络分析的结果揭示了 APOC1CCL3 小胶质细胞与 NSCs 之间的显著相互作用。与 TCGA 数据库中的 102 个潜在分子靶标进行的总生存期(OS)和无复发生存期(RFS)的相关性分析表明,与 OS(8.82%)相比,与 RFS 相关的分子数量要多得多(34.31%),其中有 9 个在临床标本中得到了验证。总之,肿瘤核心远端的 APOC1CCL3 小胶质细胞与多个分子标记的 NSCs 之间的串扰在 GBM 的复发中起一定作用。

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