Single-cell and spatial transcriptomic profiling reveals distinct tumor microenvironment dynamics in cervical adenocarcinoma and squamous cell carcinoma

作者：Yaqin Wu, Bei Wei, Zhentong Wei, Hongyan Wang, Yunyun Liu, Dongdong Xu, Xiaoming Li, Liyuan Guo, Huaiwu Lu, Huiling Shang · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-09310-2 · 被引用次数：7 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

Cervical cancer (CC), a leading cause of cancer-related deaths among women worldwide, is primarily driven by high-risk human papillomavirus (HPV) infections and comprises two major histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). Despite advances in prevention and treatment, the molecular and cellular heterogeneity of these subtypes poses significant challenges to achieving optimal clinical outcomes. Here, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to dissect the cellular and spatial heterogeneity of AC and SCC, uncovering distinct tumor microenvironment (TME) dynamics that underlie their divergent clinical behaviors. Our scRNA-seq analysis reveals that AC is enriched in epithelial cells, while SCC exhibits a more immunogenic TME with elevated plasma cells and NK/T cells. Spatial transcriptomics further highlights robust interactions between CD8 + T cells and epithelial subtypes in SCC, contrasting with the stromal-rich, immune-cold phenotype of AC. We identify subtype-specific immune and stromal features, including ICOS+ Tregs, IDO1+ cancer-associated fibroblasts (CAFs), and PLVAP+ endothelial cells, which may drive immune evasion, angiogenesis, and metastasis. These findings provide a comprehensive framework for understanding CC heterogeneity and offer actionable insights for developing subtype-specific therapeutic strategies, such as combining immune checkpoint inhibitors with stromal-targeting agents. ...