Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics
Abstract Background The progression of bladder cancer (BC) from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) significantly increases disease severity. Although the tumor microenvironment (TME) plays a pivotal role in this process, the heterogeneity of tumor cel...
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06138-6 |
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| author | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Mengzhao Zhang Ke Chen Jinhai Fan |
| author_facet | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Mengzhao Zhang Ke Chen Jinhai Fan |
| author_sort | Jianpeng Li |
| collection | DOAJ |
| description | Abstract Background The progression of bladder cancer (BC) from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) significantly increases disease severity. Although the tumor microenvironment (TME) plays a pivotal role in this process, the heterogeneity of tumor cells and TME components remains underexplored. Methods We characterized the transcriptomes of single cells from 11 BC samples, including 4 NMIBC, 4 MIBC, and 3 adjacent normal tissues. Bulk RNA-seq data were used to validate the clinical features of characteristic cells, and protein levels of these cells were further confirmed through immunohistochemistry (IHC) and multiplex immunofluorescence. Results Bladder cancer progression was associated with distinct transcriptomic features in the TME. Tumor cells in MIBC displayed enhanced glycolytic activity and downregulation of chemokines and MHC-II molecules, reducing immune cell recruitment and facilitating immune evasion. This highlights glycolysis as a potential therapeutic target for disrupting tumor progression. We identified a T cell exhaustion pathway from naive CD8 + T cells (CD8 + TCF7) to terminally exhausted CD8 + STMN1 cells, with progressively declining immune surveillance. Targeting intermediate exhaustion states may restore T cell function and improve anti-tumor immunity. Macrophages polarized toward a pro-tumorigenic phenotype, while VEGFA + mast cells promoted angiogenesis in early-stage BC, suggesting their role as potential targets for therapeutic intervention in NMIBC. Furthermore, conventional dendritic cells (DCs) transformed into LAMP3 + DCs, contributing to an immunosuppressive microenvironment and enabling immune evasion. Conclusion This study reveals dynamic changes in the TME during BC progression, including enhanced glycolysis, T cell exhaustion, and immune cell remodeling, which contribute to immune evasion and tumor progression. These findings identify critical pathways and cell populations as potential therapeutic targets, offering new strategies to improve treatment outcomes in BC patients. |
| format | Article |
| id | doaj-art-e53220b7d01e4be393d81ace8877e688 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-e53220b7d01e4be393d81ace8877e6882025-02-02T12:40:37ZengBMCJournal of Translational Medicine1479-58762025-01-0123112210.1186/s12967-025-06138-6Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomicsJianpeng Li0Yunzhong Jiang1Minghai Ma2Lu Wang3Minxuan Jing4Zezhong Yang5Mengzhao Zhang6Ke Chen7Jinhai Fan8Department of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Surgery, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background The progression of bladder cancer (BC) from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) significantly increases disease severity. Although the tumor microenvironment (TME) plays a pivotal role in this process, the heterogeneity of tumor cells and TME components remains underexplored. Methods We characterized the transcriptomes of single cells from 11 BC samples, including 4 NMIBC, 4 MIBC, and 3 adjacent normal tissues. Bulk RNA-seq data were used to validate the clinical features of characteristic cells, and protein levels of these cells were further confirmed through immunohistochemistry (IHC) and multiplex immunofluorescence. Results Bladder cancer progression was associated with distinct transcriptomic features in the TME. Tumor cells in MIBC displayed enhanced glycolytic activity and downregulation of chemokines and MHC-II molecules, reducing immune cell recruitment and facilitating immune evasion. This highlights glycolysis as a potential therapeutic target for disrupting tumor progression. We identified a T cell exhaustion pathway from naive CD8 + T cells (CD8 + TCF7) to terminally exhausted CD8 + STMN1 cells, with progressively declining immune surveillance. Targeting intermediate exhaustion states may restore T cell function and improve anti-tumor immunity. Macrophages polarized toward a pro-tumorigenic phenotype, while VEGFA + mast cells promoted angiogenesis in early-stage BC, suggesting their role as potential targets for therapeutic intervention in NMIBC. Furthermore, conventional dendritic cells (DCs) transformed into LAMP3 + DCs, contributing to an immunosuppressive microenvironment and enabling immune evasion. Conclusion This study reveals dynamic changes in the TME during BC progression, including enhanced glycolysis, T cell exhaustion, and immune cell remodeling, which contribute to immune evasion and tumor progression. These findings identify critical pathways and cell populations as potential therapeutic targets, offering new strategies to improve treatment outcomes in BC patients.https://doi.org/10.1186/s12967-025-06138-6TMEMIBCNMIBCScRNA-seqT cellEpithelial cell |
| spellingShingle | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Mengzhao Zhang Ke Chen Jinhai Fan Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics Journal of Translational Medicine TME MIBC NMIBC ScRNA-seq T cell Epithelial cell |
| title | Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics |
| title_full | Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics |
| title_fullStr | Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics |
| title_full_unstemmed | Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics |
| title_short | Epithelial cell diversity and immune remodeling in bladder cancer progression: insights from single-cell transcriptomics |
| title_sort | epithelial cell diversity and immune remodeling in bladder cancer progression insights from single cell transcriptomics |
| topic | TME MIBC NMIBC ScRNA-seq T cell Epithelial cell |
| url | https://doi.org/10.1186/s12967-025-06138-6 |
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