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

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

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180 Citations (Scopus)


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.

Original languageEnglish
Article number36956
JournalScientific reports
Publication statusPublished - 2016 Nov 14

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© The Author(s) 2016.

All Science Journal Classification (ASJC) codes

  • General


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