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

doi:10.1038/s41467-021-22890-x

	Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
	Dejima, Hitoshi 4; Hu, Xin 5; Chen, Runzhe 6; Zhang, Jiexin 7; Fujimoto, Junya 4; Parra, Edwin R.4; Haymaker, Cara 4; Hubert, Shawna M.6; Duose, Dzifa 4; Solis, Luisa M.4
刊名	NATURE COMMUNICATIONS
	2021-05-11
卷号	12
ISSN号	2041-1723
DOI	10.1038/s41467-021-22890-x
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)
英文摘要	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.
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]
WOS关键词	ATYPICAL ADENOMATOUS HYPERPLASIA ; T-CELL ; INTRATUMOR HETEROGENEITY ; MULTIPLEX IMMUNOFLUORESCENCE ; CANCER ; ROLES ; MICROENVIRONMENT ; HYPOMETHYLATION ; IMMUNOTHERAPY ; NEOANTIGENS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000658725200001
资助机构	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)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/123932]
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.Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki, Japan 2.UCL, Canc Res United Kingdom, Lung Canc Ctr Excellence, London, England 3.Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX USA 4.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA 5.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA 6.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA 7.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA 8.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 9.Univ Chinese Acad Sci, Dept Pathol, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 10.Kagoshima Univ, Dept Pathol, Grad Sch Med & Dent Sci, Kagoshima, Japan
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).