Frontiers in Immunology (Jul 2022)
Single-Cell Transcriptomics of Immune Cells Reveal Diversity and Exhaustion Signatures in Non-Small-Cell Lung Cancer
- Ying Zhao,
- Qilin Zhang,
- Kailin Tu,
- Yanmei Chen,
- Yuxuan Peng,
- Yinyun Ni,
- Guonian Zhu,
- Cheng Cheng,
- Yangqian Li,
- Xue Xiao,
- Chunyan Yu,
- Keying Lu,
- Yaxin Chen,
- Chengpin Li,
- Jun Tang,
- Gang Wang,
- Wenxin Luo,
- Wengeng Zhang,
- Guowei Che,
- Weimin Li,
- Weimin Li,
- Zhoufeng Wang,
- Dan Xie
Affiliations
- Ying Zhao
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Qilin Zhang
- Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Kailin Tu
- Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Yanmei Chen
- Health Management Center, West China Tianfu Hospital, Sichuan University, Chengdu, China
- Yuxuan Peng
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Yinyun Ni
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Guonian Zhu
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Cheng Cheng
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Yangqian Li
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Xue Xiao
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Chunyan Yu
- Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Keying Lu
- Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Yaxin Chen
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Chengpin Li
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Jun Tang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Gang Wang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Wenxin Luo
- Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Wengeng Zhang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Guowei Che
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Weimin Li
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Weimin Li
- Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Zhoufeng Wang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Dan Xie
- Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- DOI
- https://doi.org/10.3389/fimmu.2022.854724
- Journal volume & issue
-
Vol. 13
Abstract
Understanding immune cell phenotypes in the tumor microenvironment (TME) is essential for explaining and predicting progression of non-small cell lung cancer (NSCLC) and its response to immunotherapy. Here we describe the single-cell transcriptomics of CD45+ immune cells from tumors, normal tissues and blood of NSCLC patients. We identified three clusters of immune cells exerting immunosuppressive effects: CD8+ T cells with exhausted phenotype, tumor-associated macrophages (TAMs) with a pro-inflammatory M2 phenotype, and regulatory B cells (B regs) with tumor-promoting characteristics. We identified genes that may be mediating T cell phenotypes, including the transcription factors ONECUT2 and ETV4 in exhausted CD8+ T cells, TIGIT and CTL4 high expression in regulatory T cells. Our results highlight the heterogeneity of CD45+ immune cells in the TME and provide testable hypotheses about the cell types and genes that define the TME.
Keywords
- non-small cell lung cancer
- tumor microenvironment
- single-cell transcriptomic sequencing
- CD8+ T cells
- tumor-associated macrophages
- regulatory B cells
