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

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish
Article number36956
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Nov 14

Fingerprint

Head and Neck Neoplasms
Ligands
Neoplasms
Tumor-Infiltrating Lymphocytes
Squamous Cell Neoplasms
Head
T-Lymphocytes
Gene Expression Profiling
Smoking
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, Hye Ryun ; Ha, Sang Jun ; Hong, Min Hee ; Heo, Su Jin ; Koh, Yoon Woo ; Choi, Eun Chang ; Kim, Eun Kyung ; Pyo, Kyoung Ho ; Jung, Inkyung ; Seo, Daekwan ; Choi, Jaewoo ; Cho, Byoung Chul ; Yoon, Sun Och. / PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. In: Scientific reports. 2016 ; Vol. 6.
@article{b38fa11ff1ef41a599768c6d80a030e7,
title = "PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients",
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.",
author = "Kim, {Hye Ryun} and Ha, {Sang Jun} and Hong, {Min Hee} and Heo, {Su Jin} and Koh, {Yoon Woo} and Choi, {Eun Chang} and Kim, {Eun Kyung} and Pyo, {Kyoung Ho} and Inkyung Jung and Daekwan Seo and Jaewoo Choi and Cho, {Byoung Chul} and Yoon, {Sun Och}",
year = "2016",
month = "11",
day = "14",
doi = "10.1038/srep36956",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. / Kim, Hye Ryun; Ha, Sang Jun; Hong, Min Hee; Heo, Su Jin; Koh, Yoon Woo; Choi, Eun Chang; Kim, Eun Kyung; Pyo, Kyoung Ho; Jung, Inkyung; Seo, Daekwan; Choi, Jaewoo; Cho, Byoung Chul; Yoon, Sun Och.

In: Scientific reports, Vol. 6, 36956, 14.11.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

AU - Kim, Hye Ryun

AU - Ha, Sang Jun

AU - Hong, Min Hee

AU - Heo, Su Jin

AU - Koh, Yoon Woo

AU - Choi, Eun Chang

AU - Kim, Eun Kyung

AU - Pyo, Kyoung Ho

AU - Jung, Inkyung

AU - Seo, Daekwan

AU - Choi, Jaewoo

AU - Cho, Byoung Chul

AU - Yoon, Sun Och

PY - 2016/11/14

Y1 - 2016/11/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84995390559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995390559&partnerID=8YFLogxK

U2 - 10.1038/srep36956

DO - 10.1038/srep36956

M3 - Article

C2 - 27841362

AN - SCOPUS:84995390559

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 36956

ER -