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通过单细胞RNA测序和空间分析研究宫颈癌中上皮细胞与巨噬细胞的相互作用

Epithelial and macrophage cell interaction in cervical cancer through single-cell RNA-sequencing and spatial analysis.

作者信息

Wang Zhichao, Cheng Long, Li Guanghui, Cheng Huiyan

机构信息

Department of Pediatric Surgery, First Hospital of Jilin University, Changchun, Jilin, China.

Department of Intensive Care Unit, First Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Front Immunol. 2025 Apr 9;16:1537785. doi: 10.3389/fimmu.2025.1537785. eCollection 2025.

Abstract

BACKGROUND

Cervical cancer (CC) is a major global health issue, ranking sixth in cancer-related mortality. The tumor microenvironment (TME) plays a crucial role in tumor growth. This study explored the cellular composition and immunological landscape of CC using various genomic data sources.

METHODS

Data from the Cancer Genome Atlas and Gene Expression Omnibus were analyzed, including single-cell RNA sequencing, spatial transcriptome analysis, and survival data. Gene set variation analysis (GSVA) identified pathways in CD8+ cells, macrophages, and epithelial cells. Immunohistochemistry assessed marker expression in CC and normal tissues. Tumor immune dysfunction and exclusion (TIDE) scores differentiated high- and low-macrophage groups. Cell-cell communication analyses highlighted interactions between macrophages and epithelial cells.

RESULTS

Macrophage markers correlated with overall survival (OS) and disease-free survival (DFS). Epithelial cell subgroups 1 and 4, along with CD8+ T cells, were associated with OS. TIDE scores varied between groups. Specific ligand-receptor interactions were found between macrophages and epithelial cell subgroup 1. Triptolide was effective in epithelial cell subgroup 1, while memantine was more effective in macrophages.

CONCLUSION

Epithelial-macrophage interactions in the TME are crucial for CC progression and treatment, offering a potential immunotherapeutic strategy.

摘要

背景

宫颈癌(CC)是一个重大的全球健康问题,在癌症相关死亡率中排名第六。肿瘤微环境(TME)在肿瘤生长中起关键作用。本研究利用各种基因组数据源探索了CC的细胞组成和免疫格局。

方法

分析了来自癌症基因组图谱和基因表达综合数据库的数据,包括单细胞RNA测序、空间转录组分析和生存数据。基因集变异分析(GSVA)确定了CD8+细胞、巨噬细胞和上皮细胞中的通路。免疫组织化学评估了CC组织和正常组织中标志物的表达。肿瘤免疫功能障碍和排除(TIDE)评分区分了高巨噬细胞组和低巨噬细胞组。细胞间通讯分析突出了巨噬细胞和上皮细胞之间的相互作用。

结果

巨噬细胞标志物与总生存期(OS)和无病生存期(DFS)相关。上皮细胞亚群1和4以及CD8+T细胞与OS相关。TIDE评分在不同组之间有所不同。在巨噬细胞和上皮细胞亚群1之间发现了特定的配体-受体相互作用。雷公藤内酯醇在上皮细胞亚群1中有效,而美金刚在巨噬细胞中更有效。

结论

TME中的上皮-巨噬细胞相互作用对CC的进展和治疗至关重要,提供了一种潜在的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c0/12014682/7fe0dc3d726b/fimmu-16-1537785-g001.jpg

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