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; Jianjun Zhang

doi:10.1038/s41467-019-14273-0

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 WuAgda 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, Jianjun Zhang

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

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.

Original language	English (US)
Article number	603
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14273-0
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

Bioinformatics Shared Resource
Biostatistics Resource Group
Flow Cytometry and Cellular Imaging Facility

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10.1038/s41467-019-14273-0

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Reuben, A., Zhang, J., Chiou, S. H., Gittelman, R. M., Li, J., Lee, W. C., Fujimoto, J., Behrens, C., Liu, X., Wang, F., Quek, K., Wang, C., Kheradmand, F., Chen, R., Chow, C. W., Lin, H., Bernatchez, C., Jalali, A., Hu, X., ... Zhang, J. (2020). Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nature communications, 11(1), Article 603. https://doi.org/10.1038/s41467-019-14273-0

Reuben, A , Zhang, J, Chiou, SH, Gittelman, RM, Li, J, Lee, WC, Fujimoto, J, Behrens, C, Liu, X, Wang, F, Quek, K, Wang, C, Kheradmand, F, Chen, R, Chow, CW, Lin, H, Bernatchez, C, Jalali, A, Hu, X, Wu, CJ, Eterovic, AK, Parra, ER, Yusko, E, Emerson, R, Benzeno, S, Vignali, M, Wu, X, Ye, Y, Little, LD, Gumbs, C, Mao, X , Song, X, Tippen, S, Thornton, RL, Cascone, T, Snyder, A, Wargo, JA, Herbst, R, Swisher, S , Kadara, H , Moran, C , Kalhor, N, Zhang, J, Scheet, P , Vaporciyan, AA, Sepesi, B, Gibbons, DL, Robins, H, Hwu, P, Heymach, JV , Sharma, P , Allison, JP, Baladandayuthapani, V, Lee, JJ, Davis, MM, Wistuba, II , Futreal, PA & Zhang, J 2020, 'Comprehensive T cell repertoire characterization of non-small cell lung cancer', Nature communications, vol. 11, no. 1, 603. https://doi.org/10.1038/s41467-019-14273-0

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title = "Comprehensive T cell repertoire characterization of non-small cell lung cancer",

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.",

author = "Alexandre Reuben and Jiexin Zhang and Chiou, {Shin Heng} and Gittelman, {Rachel M.} and Jun Li and Lee, {Won Chul} and Junya Fujimoto and Carmen Behrens and Xiaoke Liu and Feng Wang and Kelly Quek and Chunlin Wang and Farrah Kheradmand and Runzhe Chen and Chow, {Chi Wan} and Heather Lin and Chantale Bernatchez and Ali Jalali and Xin Hu and Wu, {Chang Jiun} and Eterovic, {Agda Karina} and Parra, {Edwin Roger} and Erik Yusko and Ryan Emerson and Sharon Benzeno and Marissa Vignali and Xifeng Wu and Yuanqing Ye and Little, {Latasha D.} and Curtis Gumbs and Xizeng Mao and Xingzhi Song and Samantha Tippen and Thornton, {Rebecca L.} and Tina Cascone and Alexandra Snyder and Wargo, {Jennifer A.} and Roy Herbst and Stephen Swisher and Humam Kadara and Cesar Moran and Neda Kalhor and Jianhua Zhang and Paul Scheet and Vaporciyan, {Ara A.} and Boris Sepesi and Gibbons, {Don L.} and Harlan Robins and Patrick Hwu and Heymach, {John V.} and Padmanee Sharma and Allison, {James P.} and Veera Baladandayuthapani and Lee, {Jack J.} and Davis, {Mark M.} and Wistuba, {Ignacio I.} and Futreal, {P. Andrew} and Jianjun Zhang",

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AU - Reuben, Alexandre

AU - Zhang, Jiexin

AU - Chiou, Shin Heng

AU - Gittelman, Rachel M.

AU - Li, Jun

AU - Lee, Won Chul

AU - Fujimoto, Junya

AU - Behrens, Carmen

AU - Liu, Xiaoke

AU - Wang, Feng

AU - Quek, Kelly

AU - Wang, Chunlin

AU - Kheradmand, Farrah

AU - Chen, Runzhe

AU - Chow, Chi Wan

AU - Lin, Heather

AU - Bernatchez, Chantale

AU - Jalali, Ali

AU - Hu, Xin

AU - Wu, Chang Jiun

AU - Eterovic, Agda Karina

AU - Parra, Edwin Roger

AU - Yusko, Erik

AU - Emerson, Ryan

AU - Benzeno, Sharon

AU - Vignali, Marissa

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - Little, Latasha D.

AU - Gumbs, Curtis

AU - Mao, Xizeng

AU - Song, Xingzhi

AU - Tippen, Samantha

AU - Thornton, Rebecca L.

AU - Cascone, Tina

AU - Snyder, Alexandra

AU - Wargo, Jennifer A.

AU - Herbst, Roy

AU - Swisher, Stephen

AU - Kadara, Humam

AU - Moran, Cesar

AU - Kalhor, Neda

AU - Zhang, Jianhua

AU - Scheet, Paul

AU - Vaporciyan, Ara A.

AU - Sepesi, Boris

AU - Gibbons, Don L.

AU - Robins, Harlan

AU - Hwu, Patrick

AU - Heymach, John V.

AU - Sharma, Padmanee

AU - Allison, James P.

AU - Baladandayuthapani, Veera

AU - Lee, Jack J.

AU - Davis, Mark M.

AU - Wistuba, Ignacio I.

AU - Futreal, P. Andrew

AU - Zhang, Jianjun

PY - 2020/12/1

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N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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