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

Dejima, Hitoshi; Hu, Xin; Chen, Runzhe; Zhang, Jiexin; Fujimoto, Junya; Parra, Edwin R; Haymaker, Cara; ... Zhang, Jianjun; + view all (2021) Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features. Nature Communications , 12 (1) , Article 2722. 10.1038/s41467-021-22890-x. Green open access

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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.

Type: Article
Title: Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-021-22890-x
Publisher version: https://doi.org/10.1038/s41467-021-22890-x
Language: English
Additional information: © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10160828
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