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Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages

Author

Listed:
  • Yue Zhao

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Jian Gao

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University
    International Human Phenome Institutes (Shanghai))

  • Jun Wang

    (Fudan University)

  • Fanfan Fan

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Chao Cheng

    (West China Hospital of Sichuan University)

  • Danwen Qian

    (University College London Cancer Institute
    University College London Cancer Institute)

  • Ran Guo

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yang Zhang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Ting Ye

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Marcellus Augustine

    (University College London Cancer Institute
    University College London Cancer Institute
    University College London)

  • Yicong Lin

    (Fudan University
    Fudan University Shanghai Cancer Center)

  • Jun Shang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Hang Li

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yunjian Pan

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Qingyuan Huang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Haiqing Chen

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Han Han

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Zhendong Gao

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Qiming Wang

    (Fudan University)

  • Shiyue Zhang

    (Fudan University)

  • Mou Zhang

    (Fudan University)

  • Fangqiu Fu

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yueren Yan

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Shanila Fernandez Patel

    (University College London Cancer Institute
    University College London Cancer Institute)

  • Roberto Vendramin

    (University College London Cancer Institute
    University College London Cancer Institute)

  • Hui Yuan

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yawei Zhang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Jiaqing Xiang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Hong Hu

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yihua Sun

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

  • Yuan Li

    (Fudan University
    Fudan University Shanghai Cancer Center)

  • Kevin Litchfield

    (University College London Cancer Institute
    University College London Cancer Institute)

  • Zhiwei Cao

    (International Human Phenome Institutes (Shanghai)
    Fudan University)

  • Haiquan Chen

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

Abstract

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Suggested Citation

  • Yue Zhao & Jian Gao & Jun Wang & Fanfan Fan & Chao Cheng & Danwen Qian & Ran Guo & Yang Zhang & Ting Ye & Marcellus Augustine & Yicong Lin & Jun Shang & Hang Li & Yunjian Pan & Qingyuan Huang & Haiqin, 2024. "Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52139-2
    DOI: 10.1038/s41467-024-52139-2
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    2. Yu Liu & Jianjun Zhang & Lin Li & Guangliang Yin & Jianhua Zhang & Shan Zheng & Hannah Cheung & Ning Wu & Ning Lu & Xizeng Mao & Longhai Yang & Jiexin Zhang & Li Zhang & Sahil Seth & Huang Chen & Xing, 2016. "Genomic heterogeneity of multiple synchronous lung cancer," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
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