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

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, Hoa H. N. Pham, Nicholas Mcgranahan, Baili Zhang, Jie Ye, Lisha Ying, Latasha Little, Curtis Gumbs, Chi-Wan Chow, Marcos Roberto Estecio, Myrna C. B. Godoy, Mara B. Antonoff, Boris Sepesi, Harvey I. Pass, Carmen Behrens, Jianhua Zhang, Ara A. Vaporciyan, John V. Heymach, Paul Scheet, J. Jack Lee, Jia Wu, P. Andrew Futreal, Alexandre Reuben (), Humam Kadara (), Ignacio I. Wistuba () and Jianjun Zhang ()
Additional contact information
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
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
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
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22890-x

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