Single-Cell Proteomic Analysis Dissects the Complexity of Tumor Microenvironment in Muscle Invasive Bladder Cancer.
Single-Cell Proteomic Analysis Dissects the Complexity of Tumor Microenvironment in Muscle Invasive Bladder Cancer.
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单细胞蛋白质组分析剖析了肌层浸润性膀胱癌肿瘤微环境的复杂性。
DOI：
10.3390/cancers13215440
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发表时间：
2021-10-29
期刊：
影响因子：
5.2
通讯作者：
Mo Z
中科院分区：
文献类型：
--
作者：
Feng C;Wang X;Tao Y;Xie Y;Lai Z;Li Z;Hu J;Tang S;Pan L;He L;Wang Q;Li T;Mo Z
肿瘤微环境（tumor microenvironment， TME）被认为在许多类型肿瘤的发生发展中起着关键作用。肌肉浸润性膀胱癌（MIBC）具有高度复杂的TME，其异质性是众所周知的。在此，我们结合了质量细胞术和成像质量细胞术来系统地研究MIBC TME的复杂性。我们的研究发现肿瘤和免疫细胞具有不同的表型。我们发现了一个特定的癌症干细胞样细胞簇（ALDH+PD-L1+ER-β−），它与不良预后相关，并强调了MIBC TME成分空间分布模式的重要性。本研究全面阐明了MIBC TME的复杂性，为未来的研究提供了潜在的有价值的信息。肌浸润性膀胱癌（MIBC）是一种具有相当异质性的恶性肿瘤。MIBC肿瘤微环境（TME）是高度复杂的，包括多种表型和空间结构。必须对MIBC TME的复杂性进行表征，以提供精确治疗的潜在靶点。本研究采用肿瘤细胞术和成像细胞术相结合的方法，对44例MIBC患者的肿瘤细胞、免疫细胞和TME空间特征进行了分析。我们检测到异常表型的肿瘤和免疫细胞簇。特别是，我们发现了一种以前被忽视的癌症干细胞样细胞簇（ALDH+PD-L1+ER-β -），它与不良预后密切相关。我们阐明了免疫细胞（排除、浸润和遗弃）和肿瘤相关胶原（弯曲、拉伸、方向分布和混乱）在MIBC TME中的不同空间结构。目前的研究首次在单细胞水平上对MIBC TME的复杂性提供了深入的见解。我们的研究结果将提高对MIBC异质性特征的普遍理解，潜在地促进患者分层和个性化治疗。
The tumor microenvironment (TME) is considered to play a key role in the development of many types of tumors. Muscle invasive bladder cancer (MIBC), which is well known for its heterogeneity, has a highly complex TME. Herein, we integrated mass cytometry and imaging mass cytometry to systematically investigate the complexity of the MIBC TME. Our investigation revealed tumor and immune cells with diverse phenotypes. We identified a specific cancer stem-like cell cluster (ALDH+PD-L1+ER-β−), which is associated with poor prognosis and highlighted the importance of the spatial distribution patterns of MIBC TME components. The present study comprehensively elucidated the complexity of the MIBC TME and provides potentially valuable information for future research. Muscle invasive bladder cancer (MIBC) is a malignancy with considerable heterogeneity. The MIBC tumor microenvironment (TME) is highly complex, comprising diverse phenotypes and spatial architectures. The complexity of the MIBC TME must be characterized to provide potential targets for precision therapy. Herein, an integrated combination of mass cytometry and imaging mass cytometry was used to analyze tumor cells, immune cells, and TME spatial characteristics of 44 MIBC patients. We detected tumor and immune cell clusters with abnormal phenotypes. In particular, we identified a previously overlooked cancer stem-like cell cluster (ALDH+PD-L1+ER-β−) that was strongly associated with poor prognosis. We elucidated the different spatial architectures of immune cells (excluded, infiltrated, and deserted) and tumor-associated collagens (curved, stretched, directionally distributed, and chaotic) in the MIBC TME. The present study is the first to provide in-depth insight into the complexity of the MIBC TME at the single-cell level. Our results will improve the general understanding of the heterogeneous characteristics of MIBC, potentially facilitating patient stratification and personalized therapy.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
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。
影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
Chen K
影响因子：
5.7
作者：
Fukumoto K;Kikuchi E;Mikami S;Ogihara K;Matsumoto K;Miyajima A;Oya M
通讯作者：
Oya M
影响因子：
5.6
作者：
Asakura N;Nakamura N;Muroi A;Nojima Y;Yamashita T;Kaneko S;Ikeda K;Koshikawa N;Suzuki T
通讯作者：
Suzuki T
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
通讯作者：
Chen J