The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer
Abstract Background Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04151-1 |
| _version_ | 1827952613637750784 |
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| author | Fei Long Wei Wang Shuo Li Bicheng Wang Xin Hu Jun Wang Yaqi Xu Min Liu Junting Zhou Huaqi Si Xiaodan Xi Xiang-yu Meng Chunhui Yuan Fubing Wang |
| author_facet | Fei Long Wei Wang Shuo Li Bicheng Wang Xin Hu Jun Wang Yaqi Xu Min Liu Junting Zhou Huaqi Si Xiaodan Xi Xiang-yu Meng Chunhui Yuan Fubing Wang |
| author_sort | Fei Long |
| collection | DOAJ |
| description | Abstract Background Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. Methods Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. Results Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. Conclusions PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients. Graphical Abstract |
| first_indexed | 2024-04-09T14:00:23Z |
| format | Article |
| id | doaj.art-c48aade473144611b8f174dc0f2ad45a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T14:00:23Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-c48aade473144611b8f174dc0f2ad45a2023-05-07T11:22:11ZengBMCJournal of Translational Medicine1479-58762023-05-0121111910.1186/s12967-023-04151-1The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancerFei Long0Wei Wang1Shuo Li2Bicheng Wang3Xin Hu4Jun Wang5Yaqi Xu6Min Liu7Junting Zhou8Huaqi Si9Xiaodan Xi10Xiang-yu Meng11Chunhui Yuan12Fubing Wang13Department of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Pathology, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityCenter for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan UniversityDepartment of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversityAbstract Background Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. Methods Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. Results Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. Conclusions PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients. Graphical Abstracthttps://doi.org/10.1186/s12967-023-04151-1Cell crosstalkPlasma cellBladder cancerImmunotherapySingle-cell analysis |
| spellingShingle | Fei Long Wei Wang Shuo Li Bicheng Wang Xin Hu Jun Wang Yaqi Xu Min Liu Junting Zhou Huaqi Si Xiaodan Xi Xiang-yu Meng Chunhui Yuan Fubing Wang The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer Journal of Translational Medicine Cell crosstalk Plasma cell Bladder cancer Immunotherapy Single-cell analysis |
| title | The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| title_full | The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| title_fullStr | The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| title_full_unstemmed | The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| title_short | The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| title_sort | potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer |
| topic | Cell crosstalk Plasma cell Bladder cancer Immunotherapy Single-cell analysis |
| url | https://doi.org/10.1186/s12967-023-04151-1 |
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