Comprehensive T cell repertoire characterization of non-small cell lung cancer

Alexandre Reuben, Jiexin Zhang, Shin-Heng Chiou, Rachel M. Gittelman, Jun Li, Won-Chul Lee, Junya Fujimoto, Carmen Behrens, Xiaoke Liu, Feng Wang, Kelly Quek, Chunlin Wang, Farrah Kheradmand, Runzhe Chen, Chi-Wan Chow, Heather Lin, Chantale Bernatchez, Ali Jalali, Xin Hu, Chang-Jiun Wu, Agda Karina Eterovic, Edwin Roger Parra, Erik Yusko, Ryan Emerson, Sharon Benzeno, Marissa Vignali, Xifeng Wu, Yuanqing Ye, Latasha D. Little, Curtis Gumbs, Xizeng Mao, Xingzhi Song, Samantha Tippen, Rebecca L. Thornton, Tina Cascone, Alexandra Snyder, Jennifer A. Wargo, Roy Herbst, Stephen Swisher, Humam Kadara, Cesar Moran, Neda Kalhor, Jianhua Zhang, Paul Scheet, Ara A. Vaporciyan, Boris Sepesi, Don L. Gibbons, Harlan Robins, Patrick Hwu, John V. Heymach, Padmanee Sharma, James P. Allison, Veera Baladandayuthapani, Jack J. Lee, Mark M. Davis (), Ignacio I. Wistuba (), P. Andrew Futreal () and Jianjun Zhang ()
Additional contact information
Alexandre Reuben: The University of Texas MD Anderson Cancer Center
Jiexin Zhang: The University of Texas MD Anderson Cancer Center
Shin-Heng Chiou: Institute for Immunity, Transplantation, and Infection Operations, Howard Hughes Medical Institute
Rachel M. Gittelman: Adaptive Biotechnologies
Jun Li: The University of Texas MD Anderson Cancer Center
Won-Chul Lee: The University of Texas MD Anderson Cancer Center
Junya Fujimoto: The University of Texas MD Anderson Cancer Center
Carmen Behrens: The University of Texas MD Anderson Cancer Center
Xiaoke Liu: The University of Texas MD Anderson Cancer Center
Feng Wang: The University of Texas MD Anderson Cancer Center
Kelly Quek: The University of Texas MD Anderson Cancer Center
Chunlin Wang: iRepertoire, Inc.
Farrah Kheradmand: Baylor College of Medicine
Runzhe Chen: The University of Texas MD Anderson Cancer Center
Chi-Wan Chow: The University of Texas MD Anderson Cancer Center
Heather Lin: The University of Texas MD Anderson Cancer Center
Chantale Bernatchez: The University of Texas MD Anderson Cancer Center
Ali Jalali: The University of Texas MD Anderson Cancer Center
Xin Hu: The University of Texas MD Anderson Cancer Center
Chang-Jiun Wu: The University of Texas MD Anderson Cancer Center
Agda Karina Eterovic: The University of Texas MD Anderson Cancer Center
Edwin Roger Parra: The University of Texas MD Anderson Cancer Center
Erik Yusko: Adaptive Biotechnologies
Ryan Emerson: Adaptive Biotechnologies
Sharon Benzeno: Adaptive Biotechnologies
Marissa Vignali: Adaptive Biotechnologies
Xifeng Wu: The University of Texas MD Anderson Cancer Center
Yuanqing Ye: 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
Xizeng Mao: The University of Texas MD Anderson Cancer Center
Xingzhi Song: The University of Texas MD Anderson Cancer Center
Samantha Tippen: The University of Texas MD Anderson Cancer Center
Rebecca L. Thornton: The University of Texas MD Anderson Cancer Center
Tina Cascone: The University of Texas MD Anderson Cancer Center
Alexandra Snyder: Adaptive Biotechnologies
Jennifer A. Wargo: The University of Texas MD Anderson Cancer Center
Roy Herbst: 333 Cedar Street, Yale Cancer Center
Stephen Swisher: The University of Texas MD Anderson Cancer Center
Humam Kadara: The University of Texas MD Anderson Cancer Center
Cesar Moran: The University of Texas MD Anderson Cancer Center
Neda Kalhor: The University of Texas MD Anderson Cancer Center
Jianhua Zhang: The University of Texas MD Anderson Cancer Center
Paul Scheet: The University of Texas MD Anderson Cancer Center
Ara A. Vaporciyan: The University of Texas MD Anderson Cancer Center
Boris Sepesi: The University of Texas MD Anderson Cancer Center
Don L. Gibbons: The University of Texas MD Anderson Cancer Center
Harlan Robins: Adaptive Biotechnologies
Patrick Hwu: The University of Texas MD Anderson Cancer Center
John V. Heymach: The University of Texas MD Anderson Cancer Center
Padmanee Sharma: The University of Texas MD Anderson Cancer Center
James P. Allison: The University of Texas MD Anderson Cancer Center
Veera Baladandayuthapani: The University of Texas MD Anderson Cancer Center
Jack J. Lee: The University of Texas MD Anderson Cancer Center
Mark M. Davis: Howard Hughes Medical Institute, Stanford
Ignacio I. Wistuba: The University of Texas MD Anderson Cancer Center
P. Andrew Futreal: The University of Texas MD Anderson Cancer Center
Jianjun Zhang: The University of Texas MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.

Date: 2020
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DOI: 10.1038/s41467-019-14273-0

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