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Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients

Author

Listed:
  • Tong Liu

    (Harbin Medical University Cancer Hospital, Harbin, China; Heilongjiang Academy of Medical Sciences)

  • Cheng Liu

    (Peking University Health Science Center
    Peking University Health Science Center
    Peking University Health Science Center)

  • Meisi Yan

    (Harbin Medical University)

  • Lei Zhang

    (Peking University Health Science Center
    Peking University Health Science Center
    Peking University Health Science Center)

  • Jing Zhang

    (Peking University Health Science Center
    Peking University Health Science Center
    Peking University Health Science Center)

  • Min Xiao

    (Harbin Medical University Cancer Hospital, Harbin, China; Heilongjiang Academy of Medical Sciences)

  • Zhigao Li

    (Harbin Medical University Cancer Hospital, Harbin, China; Heilongjiang Academy of Medical Sciences)

  • Xiaofan Wei

    (Peking University Health Science Center
    Peking University Health Science Center
    Peking University Health Science Center)

  • Hongquan Zhang

    (Peking University Health Science Center
    Peking University Health Science Center
    Peking University Health Science Center
    Shenzhen University School of Medicine)

Abstract

The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4+CXCL13+ T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3+ dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A+ cancer-associated fibroblasts enriched in HER2+ breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.

Suggested Citation

  • Tong Liu & Cheng Liu & Meisi Yan & Lei Zhang & Jing Zhang & Min Xiao & Zhigao Li & Xiaofan Wei & Hongquan Zhang, 2022. "Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34581-2
    DOI: 10.1038/s41467-022-34581-2
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    References listed on IDEAS

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    1. Mihriban Karaayvaz & Simona Cristea & Shawn M. Gillespie & Anoop P. Patel & Ravindra Mylvaganam & Christina C. Luo & Michelle C. Specht & Bradley E. Bernstein & Franziska Michor & Leif W. Ellisen, 2018. "Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Lei Zhang & Xin Yu & Liangtao Zheng & Yuanyuan Zhang & Yansen Li & Qiao Fang & Ranran Gao & Boxi Kang & Qiming Zhang & Julie Y. Huang & Hiroyasu Konno & Xinyi Guo & Yingjiang Ye & Songyuan Gao & Shan , 2018. "Lineage tracking reveals dynamic relationships of T cells in colorectal cancer," Nature, Nature, vol. 564(7735), pages 268-272, December.
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