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A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments

Author

Listed:
  • Yanmei Zhang

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base)
    Beijing Academy of Science and Technology)

  • Qifan Hu

    (Tsinghua University)

  • Yuquan Pei

    (Peking University Cancer Hospital and Institute)

  • Hao Luo

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Zixuan Wang

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Xinxin Xu

    (Medical School of Chinese PLA)

  • Qing Zhang

    (Beijing Academy of Science and Technology)

  • Jianli Dai

    (Beijing Academy of Science and Technology)

  • Qianqian Wang

    (Beijing Academy of Science and Technology)

  • Zilian Fan

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Yongcong Fang

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Min Ye

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Binhan Li

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Mailin Chen

    (Peking University Cancer Hospital & Institute)

  • Qi Xue

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Qingfeng Zheng

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Shulin Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Miao Huang

    (Peking University Cancer Hospital and Institute)

  • Ting Zhang

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

  • Jin Gu

    (Tsinghua University)

  • Zhuo Xiong

    (Tsinghua University
    Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing
    Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base))

Abstract

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

Suggested Citation

  • Yanmei Zhang & Qifan Hu & Yuquan Pei & Hao Luo & Zixuan Wang & Xinxin Xu & Qing Zhang & Jianli Dai & Qianqian Wang & Zilian Fan & Yongcong Fang & Min Ye & Binhan Li & Mailin Chen & Qi Xue & Qingfeng Z, 2024. "A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47737-z
    DOI: 10.1038/s41467-024-47737-z
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