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

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  • Zhaohui Chen

    (Huazhong University of Science and Technology)

  • Lijie Zhou

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

  • Lilong Liu

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

  • Yaxin Hou

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

  • Ming Xiong

    (Huazhong University of Science and Technology)

  • Yu Yang

    (Indiana University School of Medicine)

  • Junyi Hu

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

  • Ke Chen

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

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.

Suggested Citation

  • Zhaohui Chen & Lijie Zhou & Lilong Liu & Yaxin Hou & Ming Xiong & Yu Yang & Junyi Hu & Ke Chen, 2020. "Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18916-5
    DOI: 10.1038/s41467-020-18916-5
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    Cited by:

    1. Han Luo & Xuyang Xia & Li-Bin Huang & Hyunsu An & Minyuan Cao & Gyeong Dae Kim & Hai-Ning Chen & Wei-Han Zhang & Yang Shu & Xiangyu Kong & Zhixiang Ren & Pei-Heng Li & Yang Liu & Huairong Tang & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Lena Cords & Sandra Tietscher & Tobias Anzeneder & Claus Langwieder & Martin Rees & Natalie Souza & Bernd Bodenmiller, 2023. "Cancer-associated fibroblast classification in single-cell and spatial proteomics data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Chuanyuan Wei & Wei Sun & Kangjie Shen & Jingqin Zhong & Wanlin Liu & Zixu Gao & Yu Xu & Lu Wang & Tu Hu & Ming Ren & Yinlam Li & Yu Zhu & Shaoluan Zheng & Ming Zhu & Rongkui Luo & Yanwen Yang & Yingy, 2023. "Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Victoria Stary & Ram V. Pandey & Julia List & Lisa Kleissl & Florian Deckert & Julijan Kabiljo & Johannes Laengle & Vasileios Gerakopoulos & Rudolf Oehler & Lukas Watzke & Matthias Farlik & Samuel W. , 2024. "Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Xiaojun Ren & Jianqing Liang & Yiming Zhang & Ning Jiang & Yuhui Xu & Mengdi Qiu & Yiqin Wang & Bing Zhao & Xiaojun Chen, 2022. "Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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