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

Zhaohui Chen, Lijie Zhou, Lilong Liu, Yaxin Hou, Ming Xiong, Yu Yang, Junyi Hu () and Ke Chen ()
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Zhaohui Chen: Huazhong University of Science and Technology
Lijie Zhou: Huazhong University of Science and Technology
Lilong Liu: Huazhong University of Science and Technology
Yaxin Hou: Huazhong University of Science and Technology
Ming Xiong: Huazhong University of Science and Technology
Yu Yang: Indiana University School of Medicine
Junyi Hu: Huazhong University of Science and Technology
Ke Chen: Huazhong University of Science and Technology

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18916-5

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