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

doi:10.1038/s41467-021-22890-x

HFCAS OpenIR

	Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
	Dejima, Hitoshi 1; Hu, Xin 2; Chen, Runzhe 3; Zhang, Jiexin 4; Fujimoto, Junya 1; Parra, Edwin R.1; Haymaker, Cara 1; Hubert, Shawna M.3; Duose, Dzifa 1; Solis, Luisa M.1; Su, Dan 5,6; Fukuoka, Junya 7; Tabata, Kazuhiro 7; Pham, Hoa H. N.8; Mcgranahan, Nicholas 9; Zhang, Baili 1; Ye, Jie 3; Ying, Lisha 5,10; Little, Latasha 2; Gumbs, Curtis 2; Chow, Chi-Wan 1; Estecio, Marcos Roberto 11,12; Godoy, Myrna C. B.13; Antonoff, Mara B.14; Sepesi, Boris 14; Pass, Harvey, I 15; Behrens, Carmen 3; Zhang, Jianhua2 ; Vaporciyan, Ara A.14; Heymach, John, V 3; Scheet, Paul 16; Lee, J. Jack 17; Wu, Jia 3,18; Futreal, P. Andrew 2; Reuben, Alexandre 3; Kadara, Humam 1; Wistuba, Ignacio I.1; Zhang, Jianjun 2,3
	2021-05-11
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
通讯作者	Reuben, Alexandre(AReuben@mdanderson.org) ; Kadara, Humam(HKadara@mdanderson.org) ; Wistuba, Ignacio I.(IIWistuba@mdanderson.org) ; Zhang, Jianjun(JZhang20@mdanderson.org)
摘要	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.
DOI	10.1038/s41467-021-22890-x
关键词[WOS]	ATYPICAL ADENOMATOUS HYPERPLASIA ; T-CELL ; INTRATUMOR HETEROGENEITY ; MULTIPLEX IMMUNOFLUORESCENCE ; CANCER ; ROLES ; MICROENVIRONMENT ; HYPOMETHYLATION ; IMMUNOTHERAPY ; NEOANTIGENS
收录类别	SCI
语种	英语
资助项目	MD Anderson Khalifa Scholar Award ; National Cancer Institute of the National Institute of Health Research Project Grant[R01CA234629-01] ; AACR-Johnson & Johnson Lung Cancer Innovation Science Grant[18-90-52-ZHAN] ; University of Texas MD Anderson Cancer Center PreCancer Atlas Project ; MD Anderson Physician Scientist Program ; MD Anderson Lung Cancer Moon Shot Program ; Sabin Family Foundation Award ; Duncan Family Institute Cancer Prevention Research Seed Funding Program ; Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant[RP160668] ; UT Lung Specialized Programs of Research Excellence Grant[P50CA70907] ; Cancer Prevention and Research Institute of Texas (CPRIT) grant[RP150079] ; Rydin Family Research Fund ; MD Anderson Cancer Center's Epigenomics Profiling Core and its Science Park Next-Generation Sequencing Core (CPRIT Core)[RP120348]
项目资助者	MD Anderson Khalifa Scholar Award ; National Cancer Institute of the National Institute of Health Research Project Grant ; AACR-Johnson & Johnson Lung Cancer Innovation Science Grant ; University of Texas MD Anderson Cancer Center PreCancer Atlas Project ; MD Anderson Physician Scientist Program ; MD Anderson Lung Cancer Moon Shot Program ; Sabin Family Foundation Award ; Duncan Family Institute Cancer Prevention Research Seed Funding Program ; Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant ; UT Lung Specialized Programs of Research Excellence Grant ; Cancer Prevention and Research Institute of Texas (CPRIT) grant ; Rydin Family Research Fund ; MD Anderson Cancer Center's Epigenomics Profiling Core and its Science Park Next-Generation Sequencing Core (CPRIT Core)
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000658725200001
出版者	NATURE RESEARCH
引用统计	被引频次：68[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/123933
专题	中国科学院合肥物质科学研究院
通讯作者	Reuben, Alexandre; Kadara, Humam; Wistuba, Ignacio I.; Zhang, Jianjun
作者单位	1.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA 2.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA 3.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA 4.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA 5.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 6.Univ Chinese Acad Sci, Dept Pathol, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 7.Kagoshima Univ, Dept Pathol, Grad Sch Med & Dent Sci, Kagoshima, Japan 8.Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki, Japan 9.UCL, Canc Res United Kingdom, Lung Canc Ctr Excellence, London, England 10.Univ Chinese Acad Sci, Zhejiang Canc Res Inst, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 11.Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Houston, TX USA 12.Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX USA 13.Univ Texas MD Anderson Canc Ctr, Dept Thorac Imaging, Houston, TX USA 14.Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX USA 15.New York Univ, Dept Cardiothorac Surg, Langone Med Ctr, New York, NY USA 16.Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA 17.Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA 18.Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA
推荐引用方式 GB/T 7714	Dejima, Hitoshi,Hu, Xin,Chen, Runzhe,et al. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features[J]. NATURE COMMUNICATIONS,2021,12.
APA	Dejima, Hitoshi.,Hu, Xin.,Chen, Runzhe.,Zhang, Jiexin.,Fujimoto, Junya.,...&Zhang, Jianjun.(2021).Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features.NATURE COMMUNICATIONS,12.
MLA	Dejima, Hitoshi,et al."Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features".NATURE COMMUNICATIONS 12(2021).