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

	Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer
	Chen, Ming 15,17,18,19; Chen, Runzhe 1,15,20; Jin, Ying 17,18,19; Li, Jun 1; Hu, Xin 1; Zhang, Jiexin 2; Fujimoto, Junya 3; Hubert, Shawna M.1,20; Gay, Carl M.20; Zhu, Bo 1,20
刊名	NATURE COMMUNICATIONS
	2021-11-17
卷号	12
DOI	10.1038/s41467-021-26821-8
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)
英文摘要	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.
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]
WOS关键词	INTRATUMOR HETEROGENEITY ; MUTATIONAL PROCESSES ; SENSITIVE DETECTION ; TUMOR ; NEOANTIGENS ; EXPRESSION ; SIGNATURES ; EVOLUTION ; MICROENVIRONMENT ; ADENOCARCINOMAS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PORTFOLIO
WOS记录号	WOS:000720063500020
资助机构	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)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126520]
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.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA 2.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA 3.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA 4.UCL, Canc Res United Kingdom, Lung Canc Ctr Excellence, London WC1E 6BT, England 5.Univ Cologne, Fac Med, Dept Translat Genom, D-50931 Cologne, Germany 6.Univ Hosp Cologne, Dept Otorhinolaryngol Head & Neck Surg, D-50937 Cologne, Germany 7.Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki, Japan 8.Univ Texas MD Anderson Canc Ctr, Dept Image Phys, Houston, TX 77030 USA 9.Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA 10.Baylor Coll Med, Inst Clin & Translat Res, Houston, TX 77030 USA
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).