Chen, Ming, Chen, Runzhe, Jin, Ying, Li, Jun, Hu, Xin, Zhang, Jiexin, Fujimoto, Junya, Hubert, Shawna M., Gay, Carl M., Zhu, Bo, Tian, Yanhua, McGranahan, Nicholas, Lee, Won-Chul, George, Julie, Hu, Xiao, Chen, Yamei, Wu, Meijuan, Behrens, Carmen, Chow, Chi-Wan, Pham, Hoa H. N., Fukuoka, Junya, Wu, Jia, Parra, Edwin Roger, Little, Latasha D., Gumbs, Curtis, Song, Xingzhi, Wu, Chang-Jiun, Diao, Lixia, Wang, Qi, Cardnell, Robert, Zhang, Jianhua, Wang, Jing, Le, Xiuning, Gibbons, Don L., Heymach, John, V, Lee, J. Jack, William, William N., Jr., Cheng, Chao, Glisson, Bonnie, Wistuba, Ignacio, Futreal, P. Andrew, Thomas, Roman K., Reuben, Alexandre, Byers, Lauren A. and 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. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Chen, MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, RunzheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jin, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, XinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, JiexinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fujimoto, JunyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hubert, Shawna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gay, Carl M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, BoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tian, YanhuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGranahan, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Won-ChulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, XiaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, YameiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, MeijuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrens, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chow, Chi-WanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pham, Hoa H. N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fukuoka, JunyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, JiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parra, Edwin RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Little, Latasha D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gumbs, CurtisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Song, XingzhiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Chang-JiunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diao, LixiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cardnell, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, JianhuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le, XiuningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gibbons, Don L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heymach, John, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, J. JackUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
William, William N., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheng, ChaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glisson, BonnieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wistuba, IgnacioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Futreal, P. AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuben, AlexandreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Byers, Lauren A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, JianjunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602553
DOI: 10.1038/s41467-021-26821-8
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTRATUMOR HETEROGENEITY; MUTATIONAL PROCESSES; SENSITIVE DETECTION; TUMOR; NEOANTIGENS; EXPRESSION; SIGNATURES; EVOLUTION; MICROENVIRONMENT; ADENOCARCINOMASMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60255

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