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PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

Authors
 Hye Ryun Kim  ;  Sang-Jun Ha  ;  Min Hee Hong  ;  Su Jin Heo  ;  Yoon Woo Koh  ;  Eun Chang Choi  ;  Eun Kyung Kim  ;  Kyoung Ho Pyo  ;  Inkyung Jung  ;  Daekwan Seo  ;  Jaewoo Choi  ;  Byoung Chul Cho  ;  Sun Och Yoon 
Citation
 Scientific Reports, Vol.6 : 36956, 2016 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2016
MeSH
Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/metabolism ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/metabolism* ; Carcinoma, Squamous Cell/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/metabolism* ; Head and Neck Neoplasms/pathology ; Humans ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Young Adult
Abstract
To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.
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DOI
10.1038/srep36956
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
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) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kho, Yoon Woo(고윤우)
Kim, Eun-Kyung(김은경) ORCID logo https://orcid.org/0000-0002-3368-5013
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
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
Choi, Eun Chang(최은창)
Pyo, Kyoung Ho(표경호) ORCID logo https://orcid.org/0000-0001-5428-0288
Heo, Su Jin(허수진) ORCID logo https://orcid.org/0000-0002-0615-5869
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152793
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