High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis. (May 2016)

• Record Type: Journal Article
• Authors: Finkelmeier, Fabian; Canli, Özge; Tal, Andrea; Pleli, Thomas; Trojan, Jörg; Schmidt, Michael; Kronenberger, Bernd; Zeuzem, Stefan; Piiper, Albrecht; Greten, Florian R.; Waidmann, Oliver
• Is Part Of: European journal of cancer. Volume 59(2016)
• Page Start: 152
• Page End: 159
• Publication Date: 2016-05
• Subjects: sPDL-1 -- Cirrhosis -- Hepatocellular carcinoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2016.03.002
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Aim: Immunotherapy in cancer is a recent and very promising approach, namely the inhibition of the PD/programmed death-ligand 1 (PD-L1) axis. Here we aimed to investigate the prognostic value of a soluble form of PD-L1 in hepatocellular carcinoma (HCC) patients. Methods: HCC patients were prospectively recruited and soluble programmed death-ligand 1 (sPD-L1) levels were determined. sPD-L1 levels were compared to stages of cirrhosis and HCC. The association of the sPD-L1 levels and overall survival (OS) was assessed. Results: Two hundred fifteen patients with HCC were prospectively included. The median serum sPD-L1 concentration in patients with HCC was 0.5 ng/ml (range 0.03–6.04). Soluble PD-L1 levels positively correlated with the stage of cirrhosis and with stages of HCC. Furthermore, sPD-L1 correlated positively with a marker of macrophage activation (sCD163) and inflammation (C-reactive protein). The cut-off for high-level sPD-L1 (>0.8 ng/ml) was defined by sPD-L1 levels determined in a healthy control cohort. Patients with high serum sPD-L1 concentrations had an increased mortality risk (hazard ratio 3.340, 95 % confidence interval 1.609–6.934, P < 0.001), while very low PD-L1 levels seem to come along with better prognosis. High sPD-L1 levels were associated with mortality independently from cirrhosis stage, alpha-fetoprotein and sCD163 levels in a multivariate Cox regression model. Conclusions: We conclude that a high sPD-L1 level is a possible prognostic indicator for a poor outcome in HCC patients. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future. Highlights: In hepatocellular carcinoma (HCC) anti-PD1 treatment shows the first promising results. In this work soluble programmed death-ligand 1 (sPD-L1) correlates positively with cancer stage. High sPD-L1 serum levels correlate with poor outcome and activation of innate immunity, namely sCD163. sPD-L1 is a prognostic marker in HCC patients, studies for a predictive value are warranted.