Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer

Fengying Wu, Jue Fan, Yayi He, Anwen Xiong, Jia Yu, Yixin Li, Yan Zhang, Wencheng Zhao, Fei Zhou, Wei Li, Jie Zhang, Xiaosheng Zhang, Meng Qiao, Guanghui Gao, Shanhao Chen, Xiaoxia Chen, Xuefei Li, Likun Hou, Chunyan Wu, Chunxia Su, Shengxiang Ren, Margarete Odenthal, Reinhard Buettner, Nan Fang and Caicun Zhou ()
Additional contact information
Fengying Wu: Tongji University School of Medicine
Jue Fan: Singleron Biotechnologies
Yayi He: Tongji University School of Medicine
Anwen Xiong: Tongji University School of Medicine
Jia Yu: Tongji University School of Medicine
Yixin Li: Singleron Biotechnologies
Yan Zhang: Singleron Biotechnologies
Wencheng Zhao: Tongji University School of Medicine
Fei Zhou: Tongji University School of Medicine
Wei Li: Tongji University School of Medicine
Jie Zhang: Tongji University School of Medicine
Xiaosheng Zhang: Tongji University School of Medicine
Meng Qiao: Tongji University School of Medicine
Guanghui Gao: Tongji University School of Medicine
Shanhao Chen: Tongji University School of Medicine
Xiaoxia Chen: Tongji University School of Medicine
Xuefei Li: Tongji University School of Medicine
Likun Hou: Tongji University School of Medicine
Chunyan Wu: Tongji University School of Medicine
Chunxia Su: Tongji University School of Medicine
Shengxiang Ren: Tongji University School of Medicine
Margarete Odenthal: University Hospital of Cologne
Reinhard Buettner: University Hospital of Cologne
Nan Fang: Singleron Biotechnologies
Caicun Zhou: Tongji University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.

Date: 2021
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DOI: 10.1038/s41467-021-22801-0

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