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, Zhoufeng Wang, Dan Xie
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.