Integrative single-cell analysis reveals POSTN+ fibroblast subpopulation driving immunosuppression and tumor progression in cervical cancer.
Cervical cancer remains a major global health challenge for women, with its progression closely linked to immunosuppression and complex cellular interactions within the tumor microenvironment (TME). To elucidate the heterogeneity and functional roles of fibroblast subpopulations in cervical cancer, we performed single-cell RNA sequencing on both tumor and adjacent normal tissues, identifying 11 major cell types and further subclassifying fibroblasts into 7 distinct subpopulations: MMP11+, POSTN+, PI16+, PLPP3+, SRGN+, proliferative, and antigen-presenting fibroblasts. Among these, POSTN+ fibroblasts were specifically enriched in tumor tissues and exhibited typical cancer-associated fibroblast (CAF) characteristics. Functional enrichment analysis revealed their involvement in extracellular matrix (ECM) organization, cytoskeletal regulation, HPV infection, and ECM-receptor interaction pathways. Transcription factor analysis suggested a unique regulatory network underlying this subpopulation. Cell communication analysis further demonstrated enhanced interactions between POSTN+ fibroblasts and epithelial cells in tumor tissues, indicating a potential role in promoting tumor progression or immune modulation through intercellular crosstalk. These findings highlight POSTN+ fibroblasts as a distinct CAF subpopulation within the cervical cancer TME, characterized by unique transcriptional features and active cellular communication. Their enrichment is closely associated with ECM remodeling and intercellular signaling, providing important insights into the complexity of the cervical cancer immune microenvironment and offering a basis for developing targeted therapeutic strategies.