Feng Shi and Ming Shi contributed equally to this study.
PD-1 and PD-L1 upregulation promotes CD8+ T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients
Version of Record online: 19 APR 2010
Copyright © 2010 UICC
International Journal of Cancer
Volume 128, Issue 4, pages 887–896, 15 February 2011
How to Cite
Shi, F., Shi, M., Zeng, Z., Qi, R.-Z., Liu, Z.-W., Zhang, J.-Y., Yang, Y.-P., Tien, P. and Wang, F.-S. (2011), PD-1 and PD-L1 upregulation promotes CD8+ T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int. J. Cancer, 128: 887–896. doi: 10.1002/ijc.25397
- Issue online: 19 APR 2010
- Version of Record online: 19 APR 2010
- Accepted manuscript online: 19 APR 2010 12:00AM EST
- Manuscript Accepted: 26 MAR 2010
- Manuscript Received: 25 FEB 2010
- National Key Basic Research Program of China. Grant Number: 2007CB512805
- hepatocellular carcinoma;
Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of cytotoxic CD8+ T lymphocytes, the main effector cells in hepatocellular carcinoma (HCC) patients, are not well defined. In this study, we characterized circulating and intratumor PD-1/PD-L1 expression and analyzed their association with disease progression in a cohort of hepatitis B virus-infected patients, including 56 with HCC, 20 with liver cirrhosis (LC) and 20 healthy controls (HC). The frequency of circulating PD-1+CD8+ T cells increased with disease progression from LC to HCC patients versus HC. Furthermore, tumor-infiltrating effector CD8+ T cells showed a drastic increase in PD-1 expression. These increases in circulating and intratumor PD-1+CD8+ T cells could predict poorer disease progression and postoperative recurrence. Immunohistochemical staining showed that PD-L1 expressing hepatoma cells and apoptotic infiltrating CD8+ T cells were both enriched in tumor sections. In vitro, CD8+ T cells induced PD-L1 expression on hepatoma cells in an IFN-γ–dependent manner, which in turn promoted CD8+ T cells apoptosis, and blocking PD-L1 reversed this effect. Therefore, this study extends our knowledge of the role of the PD-1/PD-L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients.