Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer
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Published:2021-11-17
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Chen Ming, Chen Runzhe, Jin Ying, Li Jun, Hu Xin, Zhang JiexinORCID, Fujimoto Junya, Hubert Shawna M.ORCID, Gay Carl M.ORCID, Zhu Bo, Tian Yanhua, McGranahan NicholasORCID, Lee Won-Chul, George JulieORCID, Hu Xiao, Chen Yamei, Wu Meijuan, Behrens Carmen, Chow Chi-Wan, Pham Hoa H. N.ORCID, Fukuoka Junya, Wu JiaORCID, Parra Edwin RogerORCID, Little Latasha D., Gumbs Curtis, Song Xingzhi, Wu Chang-JiunORCID, Diao LixiaORCID, Wang QiORCID, Cardnell Robert, Zhang JianhuaORCID, Wang JingORCID, Le XiuningORCID, Gibbons Don L.ORCID, Heymach John V.ORCID, Jack Lee J.ORCID, William William N., Cheng ChaoORCID, Glisson Bonnie, Wistuba Ignacio, Andrew Futreal P.ORCID, Thomas Roman K., Reuben AlexandreORCID, Byers Lauren A.ORCID, Zhang JianjunORCID
Abstract
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-γ 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference74 articles.
1. Howlader, N. et al. SEER Cancer Statistics Review, 1975–2016 (National Cancer Institute, 2019). 2. Alvarado-Luna, G. & Morales-Espinosa, D. Treatment for small cell lung cancer, where are we now?—a review. Transl. Lung Cancer Res. 5, 26–38 (2016). 3. Govindan, R. et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J. Clin. Oncol. 24, 4539–4544 (2006). 4. Kalemkerian, G. P. et al. Small cell lung cancer. J. Natl Compr. Canc Netw. 11, 78–98 (2013). 5. Micke, P. et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—what limits limited disease? Lung Cancer 37, 271–276 (2002).
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