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Eur J Cancer. 2016 May;59:152-159. doi: 10.1016/j.ejca.2016.03.002. Epub 2016 Mar 31.

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

Author information

1
Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Straße 42-44, D-60596 Frankfurt, Germany. Electronic address: fabian.finkelmeier@kgu.de.
2
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Straße 42-44, D-60596 Frankfurt, Germany.
3
Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
4
Institute for Transfusion Medicine and Immunohaematology Frankfurt/Main, Sandhofstraße 1, D-60528 Frankfurt, Germany.

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.

KEYWORDS:

Cirrhosis; Hepatocellular carcinoma; sPDL-1

PMID:
27039170
DOI:
10.1016/j.ejca.2016.03.002
[Indexed for MEDLINE]

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