Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma.
Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma.
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单细胞 RNA 测序强调了炎性癌症相关成纤维细胞在膀胱尿路上皮癌中的作用。
DOI：
10.1038/s41467-020-18916-5
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发表时间：
2020-10-08
影响因子：
16.6
通讯作者：
Chen K
中科院分区：
文献类型：
--
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
尽管在肿瘤生物学和治疗方面取得了实质性进展，但膀胱癌（BC）患者的临床结局仍不令人满意。肿瘤微环境（TME）是一个潜在的靶点。在这里，通过对8个BC肿瘤样品和3个帕拉肿瘤样品进行单细胞RNA测序，我们在BC微环境中鉴定了19种不同的细胞类型，表明肿瘤内的高度异质性。我们发现，肿瘤细胞下调MHC-II分子，这表明癌细胞的免疫原性下调可能有助于免疫抑制微环境的形成。我们还发现单核细胞在肿瘤区域经历M2极化并分化。此外，LAMP 3 + DC亚群可能能够募集调节性T细胞，潜在地参与免疫抑制性TME的形成。通过使用包含超过3000个BC样本的公共数据集进行相关性分析，我们确定了炎性癌症相关成纤维细胞（iCAF）在肿瘤进展中的作用，这与不良预后显著相关。此外，我们的监管网络的特点取决于iCAFs。这些结果有助于阐明iCAFs的促肿瘤机制。我们的研究结果为癌症免疫学提供了深刻的见解，并为未来的药物发现提供了重要的资源。膀胱尿路上皮癌是最常见的泌尿生殖系统癌症之一，治疗选择有限。在这里，作者使用单细胞RNA测序表征膀胱癌的肿瘤免疫微环境，并提出炎症性癌症相关成纤维细胞在肿瘤进展中的作用。
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. Bladder urothelial carcinoma is one of the most prevalent urogenital cancer types with limited therapeutic options. Here, the authors characterize the tumor immune microenvironment of bladder cancer using single cell RNA sequencing and suggest a role for inflammatory cancer-associated fibroblasts in tumor progression.
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影响因子：
16.6
作者：
Chen C;He W;Huang J;Wang B;Li H;Cai Q;Su F;Bi J;Liu H;Zhang B;Jiang N;Zhong G;Zhao Y;Dong W;Lin T
通讯作者：
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4.6
作者：
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通讯作者：
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28.2
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Kharchenko PV
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影响因子：
23.4
作者：
McConkey DJ;Choi W;Shen Y;Lee IL;Porten S;Matin SF;Kamat AM;Corn P;Millikan RE;Dinney C;Czerniak B;Siefker-Radtke AO
通讯作者：
Siefker-Radtke AO