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scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory

Author

Listed:
  • Keyong Sun

    (Tsinghua University)

  • Runda Xu

    (Tsinghua University)

  • Fuhai Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli
    Chinese Academy of Medical Sciences)

  • Naixue Yang

    (Tsinghua University
    Tsinghua University)

  • Yang Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Xiaofeng Sun

    (Tsinghua University
    Tsinghua University)

  • Peng Jin

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Wenzhe Kang

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Lemei Jia

    (Tsinghua University)

  • Jianping Xiong

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Haitao Hu

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Yantao Tian

    (Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli)

  • Xun Lan

    (Tsinghua University
    Tsinghua University
    Tsinghua University
    Tsinghua University)

Abstract

The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for tumor control but the specific characteristics for GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 GC patients with matched paratumor tissues and blood. Our results show tumor-associated stromal cells (TASCs) have upregulated activity of Wnt signaling and angiogenesis, and are negatively correlated with survival. Tumor-associated macrophages and LAMP3+ DCs are involved in mediating T cell activity and form intercellular interaction hubs with TASCs. Clonotype and trajectory analysis demonstrates that Tc17 (IL-17+CD8+ T cells) originate from tissue-resident memory T cells and can subsequently differentiate into exhausted T cells, suggesting an alternative pathway for T cell exhaustion. Our results indicate that IL17+ cells may promote tumor progression through IL17, IL22, and IL26 signaling, highlighting the possibility of targeting IL17+ cells and associated signaling pathways as a therapeutic strategy to treat GC.

Suggested Citation

  • Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32627-z
    DOI: 10.1038/s41467-022-32627-z
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    Cited by:

    1. Ruiyan Hou & Chung-Chau Hon & Yuanhua Huang, 2023. "CamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5' scRNA-seq data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Christos Miliotis & Yuling Ma & Xanthi-Lida Katopodi & Dimitra Karagkouni & Eleni Kanata & Kaia Mattioli & Nikolas Kalavros & Yered H. Pita-Juárez & Felipe Batalini & Varune R. Ramnarine & Shivani Nan, 2024. "Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Chuanyuan Wei & Wei Sun & Kangjie Shen & Jingqin Zhong & Wanlin Liu & Zixu Gao & Yu Xu & Lu Wang & Tu Hu & Ming Ren & Yinlam Li & Yu Zhu & Shaoluan Zheng & Ming Zhu & Rongkui Luo & Yanwen Yang & Yingy, 2023. "Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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