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

Chang, H.; Jung, W.; Kim, A.; Kim, H.Kyeom.; Kim, W.Bae.; Kim, J.Hoon.; Kim, B-Hui.

Apmis Acta Pathologica Microbiologica et Immunologica Scandinavica 125(8): 690-698


ISSN/ISBN: 0903-4641
PMID: 28493410
DOI: 10.1111/apm.12703
Accession: 059721698

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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.