Single-Cell Analysis of the Pan-Cancer Immune Microenvironment and scTIME Portal
Single-Cell Analysis of the Pan-Cancer Immune Microenvironment and scTIME Portal
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泛癌症免疫微环境和 scTIME 门户的单细胞分析
DOI：
10.1158/2326-6066.cir-20-1026
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发表时间：
2021-08-01
影响因子：
10.1
通讯作者：
Gao, Xin
中科院分区：
文献类型：
--
作者：
Hong, Fang;Meng, Qianqian;Gao, Xin
多个肿瘤免疫微环境（TIME）的单细胞泛癌症分析揭示了特定肿瘤类型内免疫亚群的关系，并用于开发scTIME Web门户，这是一个用户友好的工具，可供社区用于TIME分析。单细胞测序开启了肿瘤免疫微环境研究的新时代（TIME）。然而，在单细胞分辨率下，缺乏解决TIME的身份和多样性的泛癌症分析。在这里，我们首先建立了一个泛癌单细胞参考的时间与细化的亚细胞类型和识别新的细胞类型特异性转录因子。然后，我们提出了TIME共同特征的泛癌症观点，并比较了患者和肿瘤类型中每种免疫细胞类型在丰度，细胞状态和细胞通讯方面的变化。我们发现功能失调的T细胞的丰度和细胞状态是最可变的，而调节性T细胞的丰度和细胞状态是相对稳定的。肿瘤相关巨噬细胞（TAM）的一个子集，PLTP+ C1 QC + TAM，可以通过细胞因子/趋化因子信号传导调节功能失调的T细胞的丰度。TIMEs的配体-受体通讯网络具有肿瘤类型特异性，并由肿瘤富集的免疫细胞主导。我们还开发了单细胞TIME（scTIME）门户网站（http：scTIME.sklehabc.com），其中包含scTIME特定的分析模块和统一的细胞注释。除了免疫细胞组成和使用精细细胞类型分类的相关性分析外，该门户还提供细胞间相互作用和细胞类型特异性基因特征分析。我们的单细胞泛癌症分析和scTIME门户网站将提供更多关于TIME特征以及免疫治疗基础的分子和细胞机制的见解。
Single-cell, pan-cancer analysis of multiple tumor immune microenvironments (TIME) reveals the relationships of immune subsets within specific tumor types and is used to develop the scTIME Web portal, a user-friendly tool available to the community for TIME analysis. Single-cell sequencing opens a new era for the investigation of tumor immune microenvironments (TIME). However, at single-cell resolution, a pan-cancer analysis that addresses the identity and diversity of TIMEs is lacking. Here, we first built a pan-cancer single-cell reference of TIMEs with refined subcell types and recognized new cell type–specific transcription factors. We then presented a pan-cancer view of the common features of the TIME and compared the variation of each immune cell type across patients and tumor types in the aspects of abundance, cell states, and cell communications. We found that the abundance and the cell states of dysfunctional T cells were most variable, whereas those of regulatory T cells were relatively stable. A subset of tumor-associated macrophages (TAM), PLTP+C1QC+ TAMs, may regulate the abundance of dysfunctional T cells through cytokine/chemokine signaling. The ligand–receptor communication network of TIMEs was tumor-type specific and dominated by the tumor-enriched immune cells. We additionally developed the single-cell TIME (scTIME) portal (http://scTIME.sklehabc.com) with the scTIME-specific analysis modules and a unified cell annotation. In addition to the immune cell compositions and correlation analysis using refined cell type classifications, the portal also provides cell–cell interaction and cell type–specific gene signature analysis. Our single-cell pan-cancer analysis and scTIME portal will provide more insights into the features of TIMEs, as well as the molecular and cellular mechanisms underlying immunotherapies.