Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma

Hyeyoon Chang, Wonkyung Jung, Aeree Kim, Han Kyeom Kim, Wan-Bae Kim, Ji Hoon Kim, Baek-Hui Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size >5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.

Original languageEnglish
JournalAPMIS
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

CD274 Antigen
Cytotoxic T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Hepatocellular Carcinoma
Ligands
Programmed Cell Death 1 Receptor
Proteins
Serum Albumin
Cause of Death
Cell Death
Immunohistochemistry
Neoplasms

Keywords

  • Cytotoxic T lymphocyte-associated molecule-4
  • Hepatocellular carcinoma
  • Programmed cell death ligand-1
  • Programmed cell death protein 1
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Microbiology (medical)

Cite this

@article{b23b6ddd58fb4204bf4c590c677cf281,
title = "Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma",
abstract = "Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size >5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.",
keywords = "Cytotoxic T lymphocyte-associated molecule-4, Hepatocellular carcinoma, Programmed cell death ligand-1, Programmed cell death protein 1, Tumor-infiltrating lymphocytes",
author = "Hyeyoon Chang and Wonkyung Jung and Aeree Kim and Kim, {Han Kyeom} and Wan-Bae Kim and Kim, {Ji Hoon} and Baek-Hui Kim",
year = "2017",
doi = "10.1111/apm.12703",
language = "English",
journal = "Acta pathologica et microbiologica Scandinavica",
issn = "0365-5555",
publisher = "Wiley-Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma

AU - Chang, Hyeyoon

AU - Jung, Wonkyung

AU - Kim, Aeree

AU - Kim, Han Kyeom

AU - Kim, Wan-Bae

AU - Kim, Ji Hoon

AU - Kim, Baek-Hui

PY - 2017

Y1 - 2017

N2 - Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size >5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.

AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size >5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.

KW - Cytotoxic T lymphocyte-associated molecule-4

KW - Hepatocellular carcinoma

KW - Programmed cell death ligand-1

KW - Programmed cell death protein 1

KW - Tumor-infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=85019148994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019148994&partnerID=8YFLogxK

U2 - 10.1111/apm.12703

DO - 10.1111/apm.12703

M3 - Article

C2 - 28493410

AN - SCOPUS:85019148994

JO - Acta pathologica et microbiologica Scandinavica

JF - Acta pathologica et microbiologica Scandinavica

SN - 0365-5555

ER -