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Dynamic changes in circulating PD-1(+)CD8(+)T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer

 Kim, Chang Gon  ;  Hong, Min Hee  ;  Kim, Kyung Hwan  ;  Seo, In-Ho  ;  Ahn, Beung-Chul  ;  Pyo, Kyoung-Ho  ;  Synn, Chun-Bong  ;  Yoon, Hong In  ;  Shim, Hyo Sup  ;  Lee, Yong Il  ;  Choi, Seong Jin  ;  Lee, Yun Jeong  ;  Kim, Ellen Janine  ;  Kim, Youngun  ;  Kwak, Jeong-Eun  ;  Jung, Jaehyung  ;  Park, Su-Hyung  ;  Paik, Soonmyung  ;  Shin, Eui-Cheol  ;  Kim, Hye Ryun 
 EUROPEAN JOURNAL OF CANCER, Vol.143 : 113-126, 2021-01 
Journal Title
Issue Date
Anti-programmed cell death-1 treatment ; Non-small-cell lung cancer ; CD8(+) T lymphocytes ; Biomarker
Background: The predictive value of immune monitoring with circulating CD8(+) T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1(+) CD8(+) T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. Methods: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8(+) T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1(+) CD8(+) T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). Results: Circulating PD-1(+) CD8(+) T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1(+) cells among CD8(+) T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8(+) T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8(+) T lymphocytes suppresses the effector functions of tumour antigen-specific CD8(+) T lymphocytes. Conclusions: Dynamic changes in circulating PD-1(+) CD8(+) T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors. (C) 2020 Elsevier Ltd. All rights reserved.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Chang Gon(김창곤)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Shin, Ui Cheol(신의철)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Ahn, Beung-Chul(안병철) ORCID logo https://orcid.org/0000-0002-2579-2791
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Pyo, Kyoung Ho(표경호) ORCID logo https://orcid.org/0000-0001-5428-0288
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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