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 GumbsChi 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, Jianjun Zhang

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Article number2722
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

MD Anderson CCSG core facilities

  • Epigenomics Profiling Core Facility

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