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Cited by 694Bladder and Urothelial Cancer TreatmentsCancer Immunotherapy and BiomarkersImmune cells in cancer

Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma

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Chen, Zhaohui, Zhou, Lijie, Liu, Lilong, Hou, Yaxin, Xiong, Ming, Yang, Yu, Hu, Junyi, Chen, Ke·2020·Nature Communications
DOI 10.1038/s41467-020-18916-5PMC PMC7545162
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Abstract

Although substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.

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  • TBX3 is primarily expressed in malignant epithelial cells and fibroblasts at the single-cell level in BLCA.

    “we collected five BLCA samples for single-cell sequencing (named Xiangya scRNA) and found that TBX3 is primarily expressed in malignant epithelial cells and fibroblasts at the single-cell level (Figures 1E-F). The result was further validated using a public BLCA (PRJNA662018) scRNA-seq cohort 45.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [45]

    The Methods (Raw data processing and quality control) describe a bladder-cancer single-cell dataset, supporting the citation’s use to identify a validation cohort. Our copy does not identify that dataset as PRJNA662018 or report TBX3 expression in malignant epithelial cells and fibroblasts (searched: PRJNA662018, TBX3). (LLM, conf=0.78)

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References 58 · Cited by 694

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Authors
Chen, Z., Zhou, L., Liu, L., Hou, Y., Xiong, M., Yang, Y., Hu, J., & Chen, K.
Affiliations
  • Huazhong University of Science and Technology (CN)
  • Indiana University School of Medicine (US)
  • Wuhan Union Hospital (CN)
Corresponding author
  • Hu, Junyi
  • Chen, Ke
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-10-08
Volume
11
Issue
1
Pages
5077-5077
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-18916-5
PMC
PMC7545162
OpenAlex
W3092537029
Cited by
694
References
58
Citations by year
2026: 83 · 2025: 121 · 2024: 200 · 2023: 139 · 2022: 98 · 2021: 47 · 2020: 6
FWCI
68.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (2018CFA038, 81672524)
  • Natural Science Foundation of Hubei Province (2018CFA038)
  • Universidade de Macau
  • Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20180305164838833)
  • Ruijin Hospital
Topics
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
bladder urothelial carcinoma, inflammatory cancer-associated fibroblasts, tumor microenvironment, tumor-infiltrating immune cells, MHC class II downregulation, immunosuppression, M2 macrophage polarization, regulatory T cells, intratumoral heterogeneity, prognostic factors, tumor progression
MeSH terms
Cancer-Associated Fibroblasts, Urinary Bladder, Dendritic Cells, Fibroblasts, Humans, Inflammation, Ligands, Monocytes, Neoplasm Proteins, Cytokines, Cell Polarity, Sequence Analysis, RNA, Area Under Curve, Myeloid Cells, Cell Line, Tumor, Cell Proliferation, T-Lymphocytes, Regulatory, Lysosomal Membrane Proteins, Gene Regulatory Networks, DNA Copy Number Variations, Single-Cell Analysis, Tumor Microenvironment, Lysosomal-Associated Membrane Protein 3

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