AUTHOR=Zhao Ying , Zhang Qilin , Tu Kailin , Chen Yanmei , Peng Yuxuan , Ni Yinyun , Zhu Guonian , Cheng Cheng , Li Yangqian , Xiao Xue , Yu Chunyan , Lu Keying , Chen Yaxin , Li Chengpin , Tang Jun , Wang Gang , Luo Wenxin , Zhang Wengeng , Che Guowei , Li Weimin , Wang Zhoufeng , Xie Dan TITLE=Single-Cell Transcriptomics of Immune Cells Reveal Diversity and Exhaustion Signatures in Non-Small-Cell Lung Cancer JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.854724 DOI=10.3389/fimmu.2022.854724 ISSN=1664-3224 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.