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Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy

 Eun-Ah Choe  ;  Yoon Jin Cha  ;  Jae-Hwan Kim  ;  Kyoung Ho Pyo  ;  Min Hee Hong  ;  Seong Yong Park  ;  Hyo Sup Shim  ;  Inkyung Jung  ;  Chang Young Lee  ;  Byoung Chul Cho  ;  Hye Ryun Kim 
 LUNG CANCER, Vol.136 : 30-36, 2019 
Journal Title
Issue Date
CCRT ; CD8(+) tumor infiltrating lymphocyte ; PD-L1 ; Resectable NSCLC
OBJECTIVES: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome.

MATERIALS AND METHODS: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method.

RESULTS: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017).

CONCLUSIONS: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.
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1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 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 Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Seong Yong(박성용) ORCID logo https://orcid.org/0000-0002-5180-3853
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Chang Young(이창영)
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
Choe, Eun Ah(최은아) ORCID logo https://orcid.org/0000-0001-7700-8711
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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