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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

文献类型：期刊论文

作者Chen, Ming1,3,4,5; Chen, Runzhe3,6,7; Jin, Ying1,4,5; Li, Jun7; Hu, Xin7; Zhang, Jiexin8; Fujimoto, Junya9; Hubert, Shawna M.6,7; Gay, Carl M.6; Zhu, Bo6,7
刊名NATURE COMMUNICATIONS
出版日期2021-11-17
卷号12
DOI10.1038/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.
WOS关键词INTRATUMOR HETEROGENEITY ; MUTATIONAL PROCESSES ; SENSITIVE DETECTION ; TUMOR ; NEOANTIGENS ; EXPRESSION ; SIGNATURES ; EVOLUTION ; MICROENVIRONMENT ; ADENOCARCINOMAS
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)
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.Zhejiang Key Lab Radiat Oncol, Hangzhou 310022, Zhejiang, Peoples R China
2.Univ Cologne, Univ Hosp Cologne, D-50931 Cologne, Germany
3.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
4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
5.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China
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 Genom Med, Houston, TX 77030 USA
8.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA
9.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
10.UCL, Canc Res United Kingdom, Lung Canc Ctr Excellence, London WC1E 6BT, England
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).

入库方式： OAI收割

来源：合肥物质科学研究院

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