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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The authors would like to thank Macrogen for assistance with Ion AmpliSeq? Transcriptome Human Gene Expression Kit and Dong-Su Jang, a medical illustrator in the medical research support section of Yonsei University College of Medicine, Seoul, Korea, for assistance with the illustrations. This study was supported in part by a grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C1440, B. C. Cho), a Faculty Research Grant from Yonsei University College of Medicine (6-2012-0124, H.R. Kim), and a grant of the Health Fellowship Foundation (H.R. Kim).
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