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Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Author

Listed:
  • Hitoshi Dejima

    (the University of Texas MD Anderson Cancer Center)

  • Xin Hu

    (the University of Texas MD Anderson Cancer Center)

  • Runzhe Chen

    (the University of Texas MD Anderson Cancer Center)

  • Jiexin Zhang

    (the University of Texas MD Anderson Cancer Center)

  • Junya Fujimoto

    (the University of Texas MD Anderson Cancer Center)

  • Edwin R. Parra

    (the University of Texas MD Anderson Cancer Center)

  • Cara Haymaker

    (the University of Texas MD Anderson Cancer Center)

  • Shawna M. Hubert

    (the University of Texas MD Anderson Cancer Center)

  • Dzifa Duose

    (the University of Texas MD Anderson Cancer Center)

  • Luisa M. Solis

    (the University of Texas MD Anderson Cancer Center)

  • Dan Su

    (Chinese Academy of Sciences
    Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital))

  • Junya Fukuoka

    (Kagoshima University Graduate School of Medical and Dental Sciences)

  • Kazuhiro Tabata

    (Kagoshima University Graduate School of Medical and Dental Sciences)

  • Hoa H. N. Pham

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Nicholas Mcgranahan

    (Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence)

  • Baili Zhang

    (the University of Texas MD Anderson Cancer Center)

  • Jie Ye

    (the University of Texas MD Anderson Cancer Center)

  • Lisha Ying

    (Chinese Academy of Sciences
    Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital))

  • Latasha Little

    (the University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (the University of Texas MD Anderson Cancer Center)

  • Chi-Wan Chow

    (the University of Texas MD Anderson Cancer Center)

  • Marcos Roberto Estecio

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

  • Myrna C. B. Godoy

    (the University of Texas MD Anderson Cancer Center)

  • Mara B. Antonoff

    (the University of Texas MD Anderson Cancer Center)

  • Boris Sepesi

    (the University of Texas MD Anderson Cancer Center)

  • Harvey I. Pass

    (New York University Langone Medical Center)

  • Carmen Behrens

    (the University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (the University of Texas MD Anderson Cancer Center)

  • Ara A. Vaporciyan

    (the University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (the University of Texas MD Anderson Cancer Center)

  • Paul Scheet

    (the University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (the University of Texas MD Anderson Cancer Center)

  • Jia Wu

    (the University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (the University of Texas MD Anderson Cancer Center)

  • Alexandre Reuben

    (the University of Texas MD Anderson Cancer Center)

  • Humam Kadara

    (the University of Texas MD Anderson Cancer Center)

  • Ignacio I. Wistuba

    (the University of Texas MD Anderson Cancer Center)

  • Jianjun Zhang

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

Abstract

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.

Suggested Citation

  • Hitoshi Dejima & Xin Hu & Runzhe Chen & Jiexin Zhang & Junya Fujimoto & Edwin R. Parra & Cara Haymaker & Shawna M. Hubert & Dzifa Duose & Luisa M. Solis & Dan Su & Junya Fukuoka & Kazuhiro Tabata & Ho, 2021. "Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22890-x
    DOI: 10.1038/s41467-021-22890-x
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    Cited by:

    1. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Zhoufeng Wang & Zhe Li & Kun Zhou & Chengdi Wang & Lili Jiang & Li Zhang & Ying Yang & Wenxin Luo & Wenliang Qiao & Gang Wang & Yinyun Ni & Shuiping Dai & Tingting Guo & Guiyi Ji & Minjie Xu & Yiying , 2021. "Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Meng Nie & Ke Yao & Xinsheng Zhu & Na Chen & Nan Xiao & Yi Wang & Bo Peng & LiAng Yao & Peng Li & Peng Zhang & Zeping Hu, 2021. "Evolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. 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.

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