Deciphering the tumor immune microenvironment: single-cell and spatial transcriptomic insights into cervical cancer fibroblasts

作者：Zhiheng Lin, Youwei Zhou, Zhenran Liu, Wenyang Nie, Hengjie Cao, Shengnan Li, Xuanling Li, Lijun Zhu, Guangyao Lin, Yanyu Ding, Yi Jiang, Zuxi Gu, Lianwei Xu, Zhijie Zhao, Huabao Cai · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2025 · DOI：10.1186/s13046-025-03432-5 · 被引用次数：36 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

BACKGROUND: Cervical cancer (CC) remains a significant global health challenge despite advancements in screening, HPV vaccination, and therapeutic strategies. Tumor heterogeneity, driven by epigenetic modifications, affects immune evasion, metastasis, and treatment response. Cancer-associated fibroblasts (CAFs) play a crucial role in CC progression and therapy resistance. Single-cell sequencing offers new insights but remains underutilized in CC research. This study integrates single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and deconvolution analysis to identify key genes and immunotherapy targets. By constructing a prognostic model and exploring the immune microenvironment, we aim to provide novel insights into CC pathogenesis and potential therapeutic strategies. METHODS: We utilized scRNA-seq, spatial transcriptomics, deconvolution analysis, and pseudotime trajectory mapping to delineate fibroblast subtypes within the tumor immune microenvironment (TIME) of CC. Functional annotations, differential gene expression profiling, cell-cell communication pathways, and transcription factor networks were systematically analyzed. A prognostic model based on bulk RNA-seq data was constructed and validated through survival analysis, with correlations to immune microenvironment characteristics. Functional experiments investigated the role of SDC1, a critical mediator of fibroblast-tumor crosstalk. Additionally, Fibroblast-tumor cell co-culture systems and functional as...