title: High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Fabian
authors.initials: F
authors.lastname: Finkelmeier
authors.affiliation: Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Straße 42-44, D-60596 Frankfurt, Germany.
authors.forename: Özge
authors.initials: Ö
authors.lastname: Canli
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tal
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pleli
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Trojan
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology Frankfurt/Main, Sandhofstraße 1, D-60528 Frankfurt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Piiper
authors.affiliation: Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Straße 42-44, D-60596 Frankfurt, Germany.
authors.forename: Florian R
authors.initials: FR
authors.lastname: Greten
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; C423236:CD274 protein, human; D011956:Receptors, Cell Surface
keywords: Cirrhosis; Hepatocellular carcinoma; sPDL-1