High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context
Summary: Background: Despite the recent advancements in characterizing the heterogeneity of the tumour microenvironment (TME), the immunological understanding of myeloid subsets in bladder cancer (BC) remains restricted. A more comprehensive exploration of myeloid cells in BC may uncover critical i...
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Elsevier
2025-07-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425002452 |
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| author | Jiachen Liu Zhen Shi Yajian Li Jie Ma Jiaying Yao Zan Yuan Yuanhao Wang Chunyuan Yang Xiao Li Nianzeng Xing Yunping Zhu Jianhong Zhang Li Wu |
| author_facet | Jiachen Liu Zhen Shi Yajian Li Jie Ma Jiaying Yao Zan Yuan Yuanhao Wang Chunyuan Yang Xiao Li Nianzeng Xing Yunping Zhu Jianhong Zhang Li Wu |
| author_sort | Jiachen Liu |
| collection | DOAJ |
| description | Summary: Background: Despite the recent advancements in characterizing the heterogeneity of the tumour microenvironment (TME), the immunological understanding of myeloid subsets in bladder cancer (BC) remains restricted. A more comprehensive exploration of myeloid cells in BC may uncover critical immune-modulating features. Methods: We employed density gradient centrifugation to enrich the population of immune cells and collected paired tumour and normal bladder tissues from 11 patients with bladder cancer for single-cell transcriptome analysis. Additionally, in vitro cultures and mouse tumour models were further used to validate our findings. Findings: We revealed the metabolic alterations in TREM2+ macrophages and CMA1+ mast cells within BC tissues, and further demonstrated that knockout of Trem2 significantly reprogrammed the TME and upregulated PD-L1 expression on dendritic cells (DCs). Our deconvolution analysis elucidated the prognostic value of CMA1+ mast cells, CD1C+ DCs and LAMP3+ DCs in BC, as well as delineated four distinct immune cellular modules to investigate their cellular associations. Furthermore, our exploration of the interactome landscapes highlighted the anti-tumour effect of App knockdown in remodelling the TME, as well as the pivotal roles of ANNEXIN and GALECTIN pathways in BC pathogenesis. Interpretation: Our findings provide a high-resolution resource for BC, elucidating the functional myeloid cell states, including TREM2+ macrophages, CMA1+ mast cells, and CD1C+ DCs. Furthermore, our study demonstrates that TREM2 and APP function as immune-modulating molecules, with potential therapeutic implications in the context of bladder cancer. Funding: National Natural Science Foundation of China (31991174); the National Key Research and Development Program of China (2021YFA1301603 and 2023YFC2507000); the National Basic Science Center Program of China (82388101); the National Key Research and Development Program of China (2019YFA0508502 and 2022YFC2505001). |
| format | Article |
| id | doaj-art-e801d1a68ae6442ab8ec7bce75167d62 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-e801d1a68ae6442ab8ec7bce75167d622025-08-20T03:26:26ZengElsevierEBioMedicine2352-39642025-07-0111710580110.1016/j.ebiom.2025.105801High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in contextJiachen Liu0Zhen Shi1Yajian Li2Jie Ma3Jiaying Yao4Zan Yuan5Yuanhao Wang6Chunyuan Yang7Xiao Li8Nianzeng Xing9Yunping Zhu10Jianhong Zhang11Li Wu12Institute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, ChinaInstitute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, ChinaDepartment of Urology, State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Urologic Cancer Cell and Gene Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, ChinaState Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, ChinaAnnoroad Gene Technology (Beijing) Co., Ltd, Beijing, 100176, ChinaAnnoroad Gene Technology (Beijing) Co., Ltd, Beijing, 100176, ChinaInstitute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, ChinaState Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, ChinaDepartment of Urology, State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Urologic Cancer Cell and Gene Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; Corresponding author.State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China; Corresponding author.Institute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory for Immunological Research on Allergic Diseases, Tsinghua University, Beijing, 100084, China; Corresponding author. Institute for Immunology, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.Institute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory for Immunological Research on Allergic Diseases, Tsinghua University, Beijing, 100084, China; Corresponding author. Institute for Immunology, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.Summary: Background: Despite the recent advancements in characterizing the heterogeneity of the tumour microenvironment (TME), the immunological understanding of myeloid subsets in bladder cancer (BC) remains restricted. A more comprehensive exploration of myeloid cells in BC may uncover critical immune-modulating features. Methods: We employed density gradient centrifugation to enrich the population of immune cells and collected paired tumour and normal bladder tissues from 11 patients with bladder cancer for single-cell transcriptome analysis. Additionally, in vitro cultures and mouse tumour models were further used to validate our findings. Findings: We revealed the metabolic alterations in TREM2+ macrophages and CMA1+ mast cells within BC tissues, and further demonstrated that knockout of Trem2 significantly reprogrammed the TME and upregulated PD-L1 expression on dendritic cells (DCs). Our deconvolution analysis elucidated the prognostic value of CMA1+ mast cells, CD1C+ DCs and LAMP3+ DCs in BC, as well as delineated four distinct immune cellular modules to investigate their cellular associations. Furthermore, our exploration of the interactome landscapes highlighted the anti-tumour effect of App knockdown in remodelling the TME, as well as the pivotal roles of ANNEXIN and GALECTIN pathways in BC pathogenesis. Interpretation: Our findings provide a high-resolution resource for BC, elucidating the functional myeloid cell states, including TREM2+ macrophages, CMA1+ mast cells, and CD1C+ DCs. Furthermore, our study demonstrates that TREM2 and APP function as immune-modulating molecules, with potential therapeutic implications in the context of bladder cancer. Funding: National Natural Science Foundation of China (31991174); the National Key Research and Development Program of China (2021YFA1301603 and 2023YFC2507000); the National Basic Science Center Program of China (82388101); the National Key Research and Development Program of China (2019YFA0508502 and 2022YFC2505001).http://www.sciencedirect.com/science/article/pii/S2352396425002452Bladder cancerSingle-cell RNA sequencingTumour microenvironmentMyeloid cellsPrognosis |
| spellingShingle | Jiachen Liu Zhen Shi Yajian Li Jie Ma Jiaying Yao Zan Yuan Yuanhao Wang Chunyuan Yang Xiao Li Nianzeng Xing Yunping Zhu Jianhong Zhang Li Wu High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context EBioMedicine Bladder cancer Single-cell RNA sequencing Tumour microenvironment Myeloid cells Prognosis |
| title | High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context |
| title_full | High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context |
| title_fullStr | High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context |
| title_full_unstemmed | High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context |
| title_short | High-resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentResearch in context |
| title_sort | high resolution transcriptome atlas of bladder cancer highlights the functional myeloid subsets in modulating immune microenvironmentresearch in context |
| topic | Bladder cancer Single-cell RNA sequencing Tumour microenvironment Myeloid cells Prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425002452 |
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