Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma.
Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma.
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肝外胆管癌患者免疫细胞的单细胞景观
DOI：
10.1186/s12967-022-03424-5
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发表时间：
2022-05-13
影响因子：
7.4
通讯作者：
Wang, Jianming
中科院分区：
文献类型：
--
作者：
Xu, Lei;Lu, Yun;Deng, Zhengdong;Li, Xiangyu;Shi, Yuanxin;Zhao, Kai;Yao, Wei;Wang, Jianming
关键词：
肿瘤微环境（TME）中免疫细胞的复杂景观是免疫治疗的基础，但在肝外胆管癌（ECCA）中的研究明显不足。采用单细胞RNA测序技术对ECCA患者匹配的肿瘤组织、癌旁组织和外周血中的免疫细胞进行深入分析。用软件CellPhoneDB（v2.1.7）分析两个细胞群体之间的潜在细胞相互作用。我们获得了13526个细胞，并表征了ECCA中不同免疫细胞簇和亚簇的转录组和异质性，包括CD 4 + T细胞、CD 8 + T细胞、B细胞和髓系免疫细胞。我们观察到罕见的免疫细胞亚群“中间”耗尽的CD 8 + T（CD 8 + Tex）细胞和“非经典”浆细胞（CD 27 + CD 138 + CD 38 −）。此外，我们确定了潜在的免疫治疗靶点，例如，ACP 5、MAGEH 1、TNFRSF 9和CCR 8用于TcB细胞，MT 1用于CD 8 + Tex细胞。通过配体-受体分析，我们还发现Treg细胞、M2巨噬细胞和CD 8 + Tex细胞之间存在强烈的细胞相互作用，这意味着潜在的细胞交联促进了TME的免疫抑制性质。总之，本研究阐明了ECCA中TME的组成成分，揭示了ECCA中单个细胞水平上潜在的细胞间相互作用，为ECCA的免疫学研究和免疫治疗提供了新的视角。在线版本包含补充材料，可通过10.1186/s12967-022-03424-5获得。
The intricate landscape of immunocytes in the tumor microenvironment (TME) is fundamental to immunotherapy but notably under-researched in extrahepatic cholangiocarcinoma (ECCA). Single-cell RNA sequencing technology was conducted to make an in-depth analysis of immunocytes from matched tumor tissues, paratumor tissues and peripheral blood from ECCA patients. The potential cellular interactions between two cell populations were analyzed with software CellPhoneDB (v2.1.7). We obtained 13526 cells and characterized the transcriptomes and heterogeneity of different clusters and subclusters of immunocytes from ECCA, including CD4+ T cells, CD8+ T cells, B cells and myeloid immunocytes. We observed the rarely described immunocyte subclusters "intermediate" exhausted CD8+ T (CD8+ Tex) cells and “nonclassic” plasmacytes (CD27+ CD138+ CD38−). In addition, we identified potential immunotherapy targets, for example, ACP5, MAGEH1, TNFRSF9 and CCR8 for Tregs and MT1 for CD8+ Tex cells. We also found strong cellular interactions among Treg cells, M2 macrophages and CD8+ Tex cells through ligand–receptor analysis, implying that potential cellular cross-linkage promoted the immunosuppressive nature of the TME. In a word, our study illuminated the components of the TME and revealed potential cellular interactions at the individual cellular level in ECCA, we aimed to provide a new perspective for further immunological studies and immunotherapy of ECCA. The online version contains supplementary material available at 10.1186/s12967-022-03424-5.
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影响因子：
11.2
作者：
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