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

• Published in: Nature communications Vol. 11; no. 1; pp. 5077 - 12
• Main Authors: Chen, Zhaohui, Zhou, Lijie, Liu, Lilong, Hou, Yaxin, Xiong, Ming, Yang, Yu, Hu, Junyi, Chen, Ke
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.10.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Area Under Curve; Bladder; Bladder cancer; Cancer; Cancer-Associated Fibroblasts - metabolism; Cancer-Associated Fibroblasts - pathology; Cell Line, Tumor; Cell Polarity; Cell Proliferation; Correlation analysis; Cytokines - metabolism; Dendritic Cells - metabolism; DNA Copy Number Variations - genetics; Fibroblasts; Fibroblasts - pathology; Gene Regulatory Networks; Gene sequencing; Genital cancers; Heterogeneity; Humans; Immunogenicity; Immunology; Immunoregulation; Inflammation; Inflammation - pathology; Ligands; Lymphocytes; Lymphocytes T; Lysosomal Membrane Proteins - metabolism; Major histocompatibility complex; Monocytes; Monocytes - pathology; Myeloid Cells - pathology; Neoplasm Proteins - metabolism; Ribonucleic acid; RNA; Sequence Analysis, RNA; Single-Cell Analysis; Subgroups; T-Lymphocytes, Regulatory - immunology; Tumor cells; Tumor Microenvironment; Tumors; Urinary Bladder - immunology; Urinary Bladder - pathology; Urothelial carcinoma
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18916-5

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.