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多形性胶质母细胞瘤中CD8 + TIM3 + CD101 + T细胞的特征与预后分析

Characterization and prognostic of CD8 + TIM3 + CD101 + T cells in glioblastoma multiforme.

作者信息

Wang Hong-Liang, Li Sai, Ma Chun-Chun, Zheng Xiang-Hu, Wu Hao-Yuan, Chang Chen-Xi, Yang Zhi-Hao, Wang Jia-Wei, Pan Fa-Ming, Zhao Bing

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, No 678 Furong Road, Hefei Economic and Technological Development Zone, Hefei, 230000, People's Republic of China.

Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.

出版信息

Cell Biosci. 2025 May 15;15(1):60. doi: 10.1186/s13578-025-01390-1.

Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is a pervasive and aggressive malignant brain tumor. In the tumor immune microenvironment, CD8 + TIM3 + CD101 + T cells (CCT cells) play a pivotal role in tumor progression and immune evasion. This study aimed to characterize differentially expressed genes (DEGs) in CCT cells, establish a prognostic model for GBM, and explore clinical implications.

METHODS

Analysis of data from TCGA, CGGA, and GEO databases included whole-genome expression profiles, clinical data, single nucleotide mutations, and single-cell RNA sequencing. DEGs were identified, and cell trajectories were constructed using Seurat, Monocle 2, and CellChat packages. Functional enrichment analysis was conducted with clusterProfiler, and a prognostic model was developed. Immune infiltration and drug sensitivity analyses were performed to evaluate therapeutic implications.

RESULTS

Eight distinct cell types were distinguished, encompassing T cells, macrophages, neurons, mural cells, endothelial cells, oligodendrocytes, fibroblasts, and B cells. Comparative analysis revealed differences in these cell types between GBM samples with new adjuvant therapy and initial diagnosis controls. Pseudotime analysis indicated CD8 + TIM3 + CD101-T cells as precursors to CCT cells, unveiling unique gene expression patterns during this transition. The prognostic model, incorporating 22 gene features via LASSO regression, demonstrated strong predictive ability through Receiver Operating Characteristic (ROC) curves. Analysis of 28 immune cell types revealed differences between high-risk and low-risk groups, providing insights into GBM's immune evasion mechanisms. Drug sensitivity analysis proposed potential therapeutic strategies for high-risk patients.

CONCLUSION

This study offers an in-depth understanding of CCT cells in GBM, introducing a novel prognostic model and suggesting promising therapeutic approaches.

摘要

背景

多形性胶质母细胞瘤(GBM)是一种常见且侵袭性的恶性脑肿瘤。在肿瘤免疫微环境中,CD8+TIM3+CD101+T细胞(CCT细胞)在肿瘤进展和免疫逃逸中起关键作用。本研究旨在表征CCT细胞中差异表达基因(DEG),建立GBM的预后模型,并探索其临床意义。

方法

对来自TCGA、CGGA和GEO数据库的数据进行分析,包括全基因组表达谱、临床数据、单核苷酸突变和单细胞RNA测序。识别DEG,并使用Seurat、Monocle 2和CellChat软件包构建细胞轨迹。使用clusterProfiler进行功能富集分析,并建立预后模型。进行免疫浸润和药物敏感性分析以评估治疗意义。

结果

区分出八种不同的细胞类型,包括T细胞、巨噬细胞、神经元、壁细胞、内皮细胞、少突胶质细胞、成纤维细胞和B细胞。比较分析显示,接受新辅助治疗的GBM样本与初始诊断对照之间的这些细胞类型存在差异。伪时间分析表明CD8+TIM3+CD101-T细胞是CCT细胞的前体,揭示了这一转变过程中独特的基因表达模式。通过LASSO回归纳入22个基因特征的预后模型通过受试者工作特征(ROC)曲线显示出强大的预测能力。对28种免疫细胞类型的分析揭示了高风险和低风险组之间的差异,为GBM的免疫逃逸机制提供了见解。药物敏感性分析为高风险患者提出了潜在的治疗策略。

结论

本研究深入了解了GBM中的CCT细胞,引入了一种新的预后模型,并提出了有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0db/12083040/d98928f896bf/13578_2025_1390_Fig1_HTML.jpg

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