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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
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 rathe...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599854/ https://www.ncbi.nlm.nih.gov/pubmed/34789716 http://dx.doi.org/10.1038/s41467-021-26821-8 |
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| author | 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. Jack Lee, J. William, William N. Cheng, Chao Glisson, Bonnie Wistuba, Ignacio Andrew Futreal, P. Thomas, Roman K. Reuben, Alexandre Byers, Lauren A. Zhang, Jianjun |
| author_facet | 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. Jack Lee, J. William, William N. Cheng, Chao Glisson, Bonnie Wistuba, Ignacio Andrew Futreal, P. Thomas, Roman K. Reuben, Alexandre Byers, Lauren A. Zhang, Jianjun |
| author_sort | Chen, Ming |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8599854 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-85998542021-11-19 Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer 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. Jack Lee, J. William, William N. Cheng, Chao Glisson, Bonnie Wistuba, Ignacio Andrew Futreal, P. Thomas, Roman K. Reuben, Alexandre Byers, Lauren A. Zhang, Jianjun Nat Commun Article 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. Nature Publishing Group UK 2021-11-17 /pmc/articles/PMC8599854/ /pubmed/34789716 http://dx.doi.org/10.1038/s41467-021-26821-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article 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. Jack Lee, J. William, William N. Cheng, Chao Glisson, Bonnie Wistuba, Ignacio Andrew Futreal, P. Thomas, Roman K. Reuben, Alexandre Byers, Lauren A. Zhang, Jianjun Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title | Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title_full | Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title_fullStr | Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title_full_unstemmed | Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title_short | Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| title_sort | cold and heterogeneous t cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599854/ https://www.ncbi.nlm.nih.gov/pubmed/34789716 http://dx.doi.org/10.1038/s41467-021-26821-8 |
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