Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma
Abstract Background Understanding the intricate tumor microenvironment (TME) is crucial for elucidating the mechanisms underlying the progression of cervical squamous cell carcinoma (CSCC) and its response to anti-PD-1 therapy. Methods In this study, we characterized 50,649 cells obtained from the C...
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2025-03-01
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| Online Access: | https://doi.org/10.1186/s12935-025-03725-x |
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| author | Xia Li Zhao Zhao Yanmei Cheng Jiaqin Yan Fang Ren Yanyan Jia Juanhua Li Binhui Wang Junqi Liu Chenyin Wang Meimei Gao Hao Gu Mingliang Fan Huirong Shi Mei Ji Qitai Zhao |
| author_facet | Xia Li Zhao Zhao Yanmei Cheng Jiaqin Yan Fang Ren Yanyan Jia Juanhua Li Binhui Wang Junqi Liu Chenyin Wang Meimei Gao Hao Gu Mingliang Fan Huirong Shi Mei Ji Qitai Zhao |
| author_sort | Xia Li |
| collection | DOAJ |
| description | Abstract Background Understanding the intricate tumor microenvironment (TME) is crucial for elucidating the mechanisms underlying the progression of cervical squamous cell carcinoma (CSCC) and its response to anti-PD-1 therapy. Methods In this study, we characterized 50,649 cells obtained from the CSCC for single-cell RNA sequencing and integrated bulk sequencing data from The Cancer Genome Atlas (TCGA) and clinical samples to explore their cell composition, metabolic processes, signaling pathways, specific transcription factors, lineage tracking and response to immunotherapy. In vivo experiments were performed to validate the function of key cell subsets. Results We identified ten major cell type and 35 subsets of stromal and immune cells in TME and observed distinct patterns in the metabolic processes and signaling pathways of these cells between tumor and normal tissues. Furthermore, PCNA clamp-associated factor (PCLAF)+ tumor-associated epithelial cell (TAEpis) was negatively correlated with the number of C-X-C motif chemokine ligand 13 (CXCL13)+ CD8+ T cells, overall survival, and response to anti-programmed cell death-1(PD-1) therapy in patients with CSCC. Both in vivo and in vitro experiments demonstrated that PCLAF+ TAEpis promotes the apoptosis of CD8+ T and tumor growth, while also inhibiting T cell infiltration and function. Conclusion Our findings illuminate the heterogeneity of the complex TME in CSCC and offer evidence supporting PCLAF+ TAEpis as a promising therapeutic target. |
| format | Article |
| id | doaj-art-2daec59af5324bd9858b97193b17a44e |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-2daec59af5324bd9858b97193b17a44e2025-08-20T03:01:39ZengBMCCancer Cell International1475-28672025-03-0125112110.1186/s12935-025-03725-xSingle-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinomaXia Li0Zhao Zhao1Yanmei Cheng2Jiaqin Yan3Fang Ren4Yanyan Jia5Juanhua Li6Binhui Wang7Junqi Liu8Chenyin Wang9Meimei Gao10Hao Gu11Mingliang Fan12Huirong Shi13Mei Ji14Qitai Zhao15Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, the first affiliated hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Digestive System, Henan Electric Power HospitalBiotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityBiotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Understanding the intricate tumor microenvironment (TME) is crucial for elucidating the mechanisms underlying the progression of cervical squamous cell carcinoma (CSCC) and its response to anti-PD-1 therapy. Methods In this study, we characterized 50,649 cells obtained from the CSCC for single-cell RNA sequencing and integrated bulk sequencing data from The Cancer Genome Atlas (TCGA) and clinical samples to explore their cell composition, metabolic processes, signaling pathways, specific transcription factors, lineage tracking and response to immunotherapy. In vivo experiments were performed to validate the function of key cell subsets. Results We identified ten major cell type and 35 subsets of stromal and immune cells in TME and observed distinct patterns in the metabolic processes and signaling pathways of these cells between tumor and normal tissues. Furthermore, PCNA clamp-associated factor (PCLAF)+ tumor-associated epithelial cell (TAEpis) was negatively correlated with the number of C-X-C motif chemokine ligand 13 (CXCL13)+ CD8+ T cells, overall survival, and response to anti-programmed cell death-1(PD-1) therapy in patients with CSCC. Both in vivo and in vitro experiments demonstrated that PCLAF+ TAEpis promotes the apoptosis of CD8+ T and tumor growth, while also inhibiting T cell infiltration and function. Conclusion Our findings illuminate the heterogeneity of the complex TME in CSCC and offer evidence supporting PCLAF+ TAEpis as a promising therapeutic target.https://doi.org/10.1186/s12935-025-03725-xCervical squamous cell carcinomaSingle-cell RNA sequencingHeterogeneityTumor-associated epithelial cellsImmunotherapy response |
| spellingShingle | Xia Li Zhao Zhao Yanmei Cheng Jiaqin Yan Fang Ren Yanyan Jia Juanhua Li Binhui Wang Junqi Liu Chenyin Wang Meimei Gao Hao Gu Mingliang Fan Huirong Shi Mei Ji Qitai Zhao Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma Cancer Cell International Cervical squamous cell carcinoma Single-cell RNA sequencing Heterogeneity Tumor-associated epithelial cells Immunotherapy response |
| title | Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma |
| title_full | Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma |
| title_fullStr | Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma |
| title_full_unstemmed | Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma |
| title_short | Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma |
| title_sort | single cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to pd 1 blockade in cervical squamous cell carcinoma |
| topic | Cervical squamous cell carcinoma Single-cell RNA sequencing Heterogeneity Tumor-associated epithelial cells Immunotherapy response |
| url | https://doi.org/10.1186/s12935-025-03725-x |
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