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

文献类型：期刊论文

作者Dejima, Hitoshi2; Hu, Xin3; Chen, Runzhe4; Zhang, Jiexin5; Fujimoto, Junya2; Parra, Edwin R.2; Haymaker, Cara2; Hubert, Shawna M.4; Duose, Dzifa2; Solis, Luisa M.2
刊名NATURE COMMUNICATIONS
出版日期2021-05-11
卷号12
ISSN号2041-1723
DOI10.1038/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.
WOS关键词ATYPICAL ADENOMATOUS HYPERPLASIA ; T-CELL ; INTRATUMOR HETEROGENEITY ; MULTIPLEX IMMUNOFLUORESCENCE ; CANCER ; ROLES ; MICROENVIRONMENT ; HYPOMETHYLATION ; IMMUNOTHERAPY ; NEOANTIGENS
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研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000658725200001
出版者NATURE RESEARCH
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)
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.Univ Chinese Acad Sci, Dept Pathol, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China
2.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
3.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA
4.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
5.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA
6.Chinese Acad Sci, Inst Canc & Basic Med IBMC, 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
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).

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来源：合肥物质科学研究院

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