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Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer
Chen, Ming1,2,3,4; Chen, Runzhe1,5,6; Jin, Ying2,3,4; Li, Jun6; Hu, Xin6; Zhang, Jiexin7; Fujimoto, Junya8; Hubert, Shawna M.5,6; Gay, Carl M.5; Zhu, Bo5,6; Tian, Yanhua5,6; McGranahan, Nicholas9; Lee, Won-Chul6; George, Julie10,11,12; Hu, Xiao2,3,4; Chen, Yamei2,3,4; Wu, Meijuan2,3,4; Behrens, Carmen5; Chow, Chi-Wan8; Pham, Hoa H. N.13; Fukuoka, Junya13; Wu, Jia14; Parra, Edwin Roger8; Little, Latasha D.6; Gumbs, Curtis6; Song, Xingzhi6; Wu, Chang-Jiun6; Diao, Lixia7; Wang, Qi7; Cardnell, Robert5; Zhang, Jianhua6; Wang, Jing7; Le, Xiuning5; Gibbons, Don L.5; Heymach, John, V5; Lee, J. Jack15; William, William N., Jr.5; Cheng, Chao16; Glisson, Bonnie5; Wistuba, Ignacio8; Futreal, P. Andrew6; Thomas, Roman K.17,18,19,20; Reuben, Alexandre5; Byers, Lauren A.5; Zhang, Jianjun5,6
2021-11-17
Source PublicationNATURE COMMUNICATIONS
Corresponding AuthorChen, Ming(chenming@sysucc.org.cn) ; Thomas, Roman K.(roman.thomas@uni-koeln.de) ; Reuben, Alexandre(areuben@mdanderson.org) ; Byers, Lauren A.(lbyers@mdanderson.org) ; Zhang, Jianjun(jzhang20@mdanderson.org)
AbstractSmall-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, using multi-region whole exome/T cell receptor (TCR) sequencing as well as immunohistochemistry, we reveal a rather homogeneous mutational landscape but extremely cold and heterogeneous TCR repertoire in limited-stage SCLC tumors (LS-SCLCs). Compared to localized non-small cell lung cancers, LS-SCLCs have similar predicted neoantigen burden and genomic ITH, but significantly colder and more heterogeneous TCR repertoire associated with higher chromosomal copy number aberration (CNA) burden. Furthermore, copy number loss of IFN-gamma pathway genes is frequently observed and positively correlates with CNA burden. Higher mutational burden, higher T cell infiltration and positive PD-L1 expression are associated with longer overall survival (OS), while higher CNA burden is associated with shorter OS in patients with LS-SCLC. Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold and heterogeneous T cell repertoire.
DOI10.1038/s41467-021-26821-8
WOS KeywordINTRATUMOR HETEROGENEITY ; MUTATIONAL PROCESSES ; SENSITIVE DETECTION ; TUMOR ; NEOANTIGENS ; EXPRESSION ; SIGNATURES ; EVOLUTION ; MICROENVIRONMENT ; ADENOCARCINOMAS
Indexed BySCI
Language英语
Funding ProjectBarbanti Small Cell Lung Cancer Award ; Conquer Cancer Foundation ASCO Young Investigator Award ; MD Anderson Physician Scientist Award ; University Cancer Foundation Sister Institution Network Fund ; Cancer Prevention & Research Institute of Texas (CPRIT) Multiple Investigator Award ; TJ Martell Foundation ; NIH/NCI[R01-CA207295] ; NIH/NCI[U01-CA213273] ; NIH/NCI[U01-CA256780-01] ; NIH/NCI[T32 CA009666] ; Department of Defense[LC170171] ; University of Texas SPORE in Lung Cancer[P5CA070907] ; MD Anderson Cancer Center CCSG[P30CA01667] ; LUNGevity Foundation ; Rexanna Foundation for Fighting Lung Cancer ; National Natural Science Foundation of China[81672972] ; Major Project of Zhejiang Provincial Health Science Foundation[2017211789] ; German Research Foundation Deutsche Forschungsgemeinsaft (DFG, Deutsche Forschungsgemeinsaft)[SFB1399] ; German Research Foundation Deutsche Forschungsgemeinsaft (DFG, Deutsche Forschungsgemeinsaft)[413326622] ; German Ministry of Science and Education (BMBF)[01ZX1901A]
Funding OrganizationBarbanti Small Cell Lung Cancer Award ; Conquer Cancer Foundation ASCO Young Investigator Award ; MD Anderson Physician Scientist Award ; University Cancer Foundation Sister Institution Network Fund ; Cancer Prevention & Research Institute of Texas (CPRIT) Multiple Investigator Award ; TJ Martell Foundation ; NIH/NCI ; Department of Defense ; University of Texas SPORE in Lung Cancer ; MD Anderson Cancer Center CCSG ; LUNGevity Foundation ; Rexanna Foundation for Fighting Lung Cancer ; National Natural Science Foundation of China ; Major Project of Zhejiang Provincial Health Science Foundation ; German Research Foundation Deutsche Forschungsgemeinsaft (DFG, Deutsche Forschungsgemeinsaft) ; German Ministry of Science and Education (BMBF)
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000720063500020
PublisherNATURE PORTFOLIO
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.hfcas.ac.cn:8080/handle/334002/126521
Collection中国科学院合肥物质科学研究院
Corresponding AuthorChen, Ming; Thomas, Roman K.; Reuben, Alexandre; Byers, Lauren A.; Zhang, Jianjun
Affiliation1.Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Dept Radiat Oncol,Sun Yat Sen Univ Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China
2.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
3.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China
4.Zhejiang Key Lab Radiat Oncol, Hangzhou 310022, Zhejiang, Peoples R China
5.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
6.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA
7.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA
8.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
9.UCL, Canc Res United Kingdom, Lung Canc Ctr Excellence, London WC1E 6BT, England
10.Univ Cologne, Fac Med, Dept Translat Genom, D-50931 Cologne, Germany
11.Univ Cologne, Univ Hosp Cologne, D-50931 Cologne, Germany
12.Univ Hosp Cologne, Dept Otorhinolaryngol Head & Neck Surg, D-50937 Cologne, Germany
13.Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki, Japan
14.Univ Texas MD Anderson Canc Ctr, Dept Image Phys, Houston, TX 77030 USA
15.Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
16.Baylor Coll Med, Inst Clin & Translat Res, Houston, TX 77030 USA
17.Univ Cologne, Med Fac, Dept Translat Genom, D-50931 Cologne, Germany
18.Univ Hosp Cologne, Med Fac, Dept Pathol, D-50931 Cologne, Germany
19.DKFZ, German Canc Res Ctr, D-69115 Heidelberg, Germany
20.German Canc Consortium DKTK, D-69115 Heidelberg, Germany
Recommended Citation
GB/T 7714
Chen, Ming,Chen, Runzhe,Jin, Ying,et al. Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer[J]. NATURE COMMUNICATIONS,2021,12.
APA Chen, Ming.,Chen, Runzhe.,Jin, Ying.,Li, Jun.,Hu, Xin.,...&Zhang, Jianjun.(2021).Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer.NATURE COMMUNICATIONS,12.
MLA Chen, Ming,et al."Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer".NATURE COMMUNICATIONS 12(2021).
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