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

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 immunofluor...

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Veröffentlicht in:Nature communications Jg. 12; H. 1; S. 2722 - 11
Hauptverfasser: Dejima, Hitoshi, Hu, Xin, Chen, Runzhe, Zhang, Jiexin, Fujimoto, Junya, Parra, Edwin R., Haymaker, Cara, Hubert, Shawna M., Duose, Dzifa, Solis, Luisa M., Su, Dan, Fukuoka, Junya, Tabata, Kazuhiro, Pham, Hoa H. N., Mcgranahan, Nicholas, Zhang, Baili, Ye, Jie, Ying, Lisha, Little, Latasha, Gumbs, Curtis, Chow, Chi-Wan, Estecio, Marcos Roberto, Godoy, Myrna C. B., Antonoff, Mara B., Sepesi, Boris, Pass, Harvey I., Behrens, Carmen, Zhang, Jianhua, Vaporciyan, Ara A., Heymach, John V., Scheet, Paul, Lee, J. Jack, Wu, Jia, Futreal, P. Andrew, Reuben, Alexandre, Kadara, Humam, Wistuba, Ignacio I., Zhang, Jianjun
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 11.05.2021
Nature Publishing Group
Nature Portfolio
Schlagworte:
45/23
631/181/2474
631/250/580/1884/2323
631/67/1612/1350
692/4028/67/1612/1350
692/4028/67/580/1884/2323
Adenocarcinoma
Carcinogenesis
Carcinogens
Copy number
Cytotoxicity
DNA methylation
Down-regulation
Epigenetics
Evolution
Humanities and Social Sciences
Immune response
Immune system
Immunity
Immunofluorescence
Immunoregulation
Immunosuppression
Infiltration
Lung cancer
Lungs
Lymphocytes
Lymphocytes T
Metastases
multidisciplinary
Mutation
Precursors
Preneoplasia
Science
Science (multidisciplinary)
T cell receptors
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung: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. The evolution of immune landscape in lung adenocarcinoma (ADC) is largely unknown. Here the authors use a cohort of resected invasive lung ADC and its precursors and show a gradual increase of immunosuppression and decrease of anti-tumor response associated with specific genomic and epigenetic features.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-22890-x