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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

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  • Ming Chen

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University
    The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology)

  • Runzhe Chen

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University
    the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

  • Ying Jin

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology)

  • Jun Li

    (the University of Texas MD Anderson Cancer Center)

  • Xin Hu

    (the University of Texas MD Anderson Cancer Center)

  • Jiexin Zhang

    (the University of Texas MD Anderson Cancer Center)

  • Junya Fujimoto

    (the University of Texas MD Anderson Cancer Center)

  • Shawna M. Hubert

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

  • Carl M. Gay

    (the University of Texas MD Anderson Cancer Center)

  • Bo Zhu

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

  • Yanhua Tian

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

  • Nicholas McGranahan

    (Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence)

  • Won-Chul Lee

    (the University of Texas MD Anderson Cancer Center)

  • Julie George

    (Faculty of Medicine and University Hospital Cologne, University of Cologne
    Head and Neck Surgery, University Hospital Cologne)

  • Xiao Hu

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology)

  • Yamei Chen

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology)

  • Meijuan Wu

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
    Chinese Academy of Sciences
    Zhejiang Key Laboratory of Radiation Oncology)

  • Carmen Behrens

    (the University of Texas MD Anderson Cancer Center)

  • Chi-Wan Chow

    (the University of Texas MD Anderson Cancer Center)

  • Hoa H. N. Pham

    (Nagasaki University Graduate school of Biomedical Sciences)

  • Junya Fukuoka

    (Nagasaki University Graduate school of Biomedical Sciences)

  • Jia Wu

    (the University of Texas MD Anderson Cancer Center)

  • Edwin Roger Parra

    (the University of Texas MD Anderson Cancer Center)

  • Latasha D. Little

    (the University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (the University of Texas MD Anderson Cancer Center)

  • Xingzhi Song

    (the University of Texas MD Anderson Cancer Center)

  • Chang-Jiun Wu

    (the University of Texas MD Anderson Cancer Center)

  • Lixia Diao

    (the University of Texas MD Anderson Cancer Center)

  • Qi Wang

    (the University of Texas MD Anderson Cancer Center)

  • Robert Cardnell

    (the University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (the University of Texas MD Anderson Cancer Center)

  • Jing Wang

    (the University of Texas MD Anderson Cancer Center)

  • Xiuning Le

    (the University of Texas MD Anderson Cancer Center)

  • Don L. Gibbons

    (the University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (the University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (the University of Texas MD Anderson Cancer Center)

  • William N. William

    (the University of Texas MD Anderson Cancer Center)

  • Chao Cheng

    (Baylor College of Medicine)

  • Bonnie Glisson

    (the University of Texas MD Anderson Cancer Center)

  • Ignacio Wistuba

    (the University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (the University of Texas MD Anderson Cancer Center)

  • Roman K. Thomas

    (Medical Faculty, University of Cologne
    Medical Faculty, University Hospital Cologne
    DKFZ, German Cancer Research Center and German Cancer Consortium (DKTK))

  • Alexandre Reuben

    (the University of Texas MD Anderson Cancer Center)

  • Lauren A. Byers

    (the University of Texas MD Anderson Cancer Center)

  • Jianjun Zhang

    (the University of Texas MD Anderson Cancer Center
    the University of Texas MD Anderson Cancer Center)

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-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.

Suggested Citation

  • Ming Chen & Runzhe Chen & Ying Jin & Jun Li & Xin Hu & Jiexin Zhang & Junya Fujimoto & Shawna M. Hubert & Carl M. Gay & Bo Zhu & Yanhua Tian & Nicholas McGranahan & Won-Chul Lee & Julie George & Xiao , 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, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26821-8
    DOI: 10.1038/s41467-021-26821-8
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    References listed on IDEAS

    as
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