Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer

doi:10.1038/s41467-021-26821-8

HFCAS OpenIR

	Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer
	Chen, Ming 1,2,3,4; Chen, Runzhe 1,5,6; Jin, Ying 2,3,4; Li, Jun 6; Hu, Xin 6; Zhang, Jiexin 7; Fujimoto, Junya 8; Hubert, Shawna M.5,6; Gay, Carl M.5; Zhu, Bo 5,6; Tian, Yanhua 5,6; McGranahan, Nicholas 9; Lee, Won-Chul 6; George, Julie 10,11,12; Hu, Xiao 2,3,4; Chen, Yamei 2,3,4; Wu, Meijuan 2,3,4; Behrens, Carmen 5; Chow, Chi-Wan 8; Pham, Hoa H. N.13; Fukuoka, Junya 13; Wu, Jia 14; Parra, Edwin Roger 8; Little, Latasha D.6; Gumbs, Curtis 6; Song, Xingzhi 6; Wu, Chang-Jiun 6; Diao, Lixia 7; Wang, Qi 7; Cardnell, Robert 5; Zhang, Jianhua6 ; Wang, Jing 7; Le, Xiuning 5; Gibbons, Don L.5; Heymach, John, V 5; Lee, J. Jack 15; William, William N., Jr.5; Cheng, Chao 16; Glisson, Bonnie 5; Wistuba, Ignacio 8; Futreal, P. Andrew 6; Thomas, Roman K.17,18,19,20; Reuben, Alexandre 5; Byers, Lauren A.5; Zhang, Jianjun 5,6
	2021-11-17
发表期刊	NATURE COMMUNICATIONS
通讯作者	Chen, 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)
摘要	Small-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.
DOI	10.1038/s41467-021-26821-8
关键词[WOS]	INTRATUMOR HETEROGENEITY ; MUTATIONAL PROCESSES ; SENSITIVE DETECTION ; TUMOR ; NEOANTIGENS ; EXPRESSION ; SIGNATURES ; EVOLUTION ; MICROENVIRONMENT ; ADENOCARCINOMAS
收录类别	SCI
语种	英语
资助项目	Barbanti 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]
项目资助者	Barbanti 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研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000720063500020
出版者	NATURE PORTFOLIO
引用统计	被引频次：21[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/334002/126521
专题	中国科学院合肥物质科学研究院
通讯作者	Chen, Ming; Thomas, Roman K.; Reuben, Alexandre; Byers, Lauren A.; Zhang, Jianjun
作者单位	1.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
推荐引用方式 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).