Genomic and TCR Repertoire Intratumor Heterogeneity of Small-cell Lung Cancer and its Impact on Survival
Year: 2020
Type: preprint
Study design: Observational Study
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, we revealed a rather homogeneous mutational landscape but extremely suppressed and heterogeneous T cell receptor (TCR) repertoire in SCLCs. Higher mutational burden, lower chromosomal copy number aberration (CNA) burden, less CNA ITH and less TCR ITH were associated with longer overall survival of SCLC patients. Compared to non-small cell lung cancers (NSCLCs), SCLCs had similar predicted neoantigen burden and mutational ITH, but significantly more suppressed and heterogeneous TCR repertoire that may be associated with higher CNA burden and CNA ITH in SCLC. Novel therapeutic strategies targeting CNA could potentially improve the tumor immune microenvironment and response to immunotherapy in SCLC.
Authors: Ming Chen, Runzhe Chen, Ying Jin, Jun Li, Jiexin Zhang, Junya Fujimoto, Won-Chul Lee, Xin Hu, Shawna Maria Hubert, Julie George, Xiao Hu, Yamei Chen, Carmen Behrens, Chi-Wan Chow, Hoa H.N. Pham, Junya Fukuoka, Edwin Roger Parra, Carl M. Gay, Latasha D. Little, Curtis Gumbs, Xingzhi Song, Lixia Diao, Qi Wang, Robert Cardnell, Jianhua Zhang, Jing Wang, Don L. Gibbons, John V. Heymach, J. Jack Lee, William N. William, Bonnie Glisson, Ignacio Wistuba, P. Andrew Futreal, Roman K. Thomas, Alexandre Reuben, Lauren A. Byers, Jianjun Zhang
Institutions: Chinese Academy of Sciences, Zhejiang Cancer Hospital, University of Chinese Academy of Sciences, The University of Texas MD Anderson Cancer Center, University of Cologne, Nagasaki University, German Cancer Research Center, University Hospital Cologne, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Conquer Cancer Foundation, Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Cancer Prevention and Research Institute of Texas, American Society of Clinical Oncology, Innovent Biologics, National Natural Science Foundation of China, National Institutes of Health, Genentech, EMD Serono, University of Texas MD Anderson Cancer Center, National Cancer Institute
OpenAlex ID: W4232550478