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Updated: May 17, 2025
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer
Xingning Mao1,2, Rirong Yang1,3, Yunkun Yan4,5
1Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy.
Insights
Single-cell analysis reveals distinct immune cell profiles in bladder cancer, identifying LAG-3 and TIM-3 as potential new targets for immune checkpoint inhibitors and highlighting Neu-FCGR3B as a possible predictive biomarker.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Bladder cancer treatment has advanced, but underlying immune mechanisms and response to immune checkpoint inhibitors remain limited.
- Understanding the tumor immune microenvironment is crucial for developing effective bladder cancer therapies.
Purpose of the Study:
- To investigate the immunological landscape of bladder cancer using single-cell RNA sequencing.
- To identify novel therapeutic targets and biomarkers for bladder cancer immunotherapy.
Main Methods:
- Single-cell RNA sequencing of peripheral blood mononuclear cells from bladder cancer patients and healthy donors.
- Analysis of cell proportions, gene expression, and pathway enrichment.
Main Results:
- Increased proportions of T cells and neutrophils observed in bladder cancer patients.
- Elevated expression of inhibitory receptors like LAG3, HAVCR2, CTLA4, and TIGIT on specific T cell and NK cell subsets.
- Identification of Mono4-THBS1 associated with tumor hypoxia and angiogenesis, and Neu-FCGR3B with potential detrimental anti-tumor roles.
Conclusions:
- LAG-3 and TIM-3 show potential as novel immune checkpoint inhibitors for bladder cancer.
- Specific cell phenotypes (NK3-CMC1, Bcell2-TCL1A, Bcell3-MS4A1) may be modulated by tumor progression.
- Neu-FCGR3B could serve as a predictive biomarker for bladder cancer immunotherapy.
