Single cell RNA-Sequencing Reveals Mast Cells Enhance Mononuclear Phagocytes Infiltration in Bladder Cancer Microenvironment.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI:10.7150/jca.99554

Zige Liu, Caisheng Huang, Xingning Mao, Junhao Mi, Qingyun Zhang, Yuli Xie, Hao Yuan, Mujia Jili, Jiange Zhang, Jianxin Chen, Shengzhu Huang, Zengnan Mo, Rirong Yang

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Abstract

Objective: Investigating the interaction between Mast cells (MCs) and Mononuclear Phagocytes (MPs) in the tumor microenvironment (TME) of blader cancer (BCa) to uncover potential immunotherapeutic targets. Methods: Single-cell RNA sequencing (scRNA-Seq) was conducted on 12 BCa patients to identify distinct subgroups of MCs and MPs. Transcriptome data was analyzed to characterize the phenotype, gene enrichment, cell-cell communication, and biological processes. The expression levels of cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), while the chemotactic effects of cytokines were evaluated through Transwell assay. Results: In muscle-invasive bladder cancer (MIBC), the proportion of interferon-stimulated MC subtype (Mast-ISG15) increased. Mast-IL13 subgroup and Mast-CCL2 subgroups were functionally enriched in interferon (IFN) and nuclear factor kappa-B (NF-κB) signaling pathways. The Mast-CCL2 subgroup overexpressed the CCL2 gene, which could chemoattract MPs through CCL2. In vitro experiments confirmed that under stimulation, activated MCs activated IFN and NF-κB signaling, increasing the secretion of CCL2 and IL-13, chemoattracted THP-1 monocyte. Conclusion: This study revealed the vital role of MCs in shaping the TME of BCa. And provides new insights for the precise treatment of BCa.

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单细胞 RNA 序列测定揭示肥大细胞能增强膀胱癌微环境中单核吞噬细胞的浸润能力

研究目的研究乳腺癌（BCa）肿瘤微环境（TME）中肥大细胞（MCs）和单核吞噬细胞（MPs）之间的相互作用，以发现潜在的免疫治疗靶点。研究方法对 12 名 BCa 患者进行单细胞 RNA 测序（scRNA-Seq），以确定 MCs 和 MPs 的不同亚群。通过分析转录组数据来描述表型、基因富集、细胞间通讯和生物过程。细胞因子的表达水平通过酶联免疫吸附试验（ELISA）进行评估，细胞因子的趋化效应通过Transwell试验进行评估。结果在肌浸润性膀胱癌（MIBC）中，干扰素刺激的 MC 亚型（Mast-ISG15）比例增加。Mast-IL13亚组和Mast-CCL2亚组在干扰素（IFN）和核因子卡巴-B（NF-κB）信号通路中功能丰富。Mast-CCL2亚群过度表达CCL2基因，可通过CCL2趋化吸引MPs。体外实验证实，活化的 MCs 在刺激下激活 IFN 和 NF-κB 信号，增加 CCL2 和 IL-13 的分泌，对 THP-1 单核细胞产生化学吸引作用。结论本研究揭示了 MCs 在形成 BCa 的 TME 中的重要作用。并为精确治疗 BCa 提供了新的见解。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567