Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma

PLoS One. 2011;6(9):e23621. doi: 10.1371/journal.pone.0023621. Epub 2011 Sep 1.

Abstract

Background: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC).

Methodology/principal findings: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation.

Conclusions/significance: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / blood*
  • B7-H1 Antigen / metabolism
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology
  • Cryosurgery*
  • Disease Progression
  • Female
  • Hepatitis B virus / physiology*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / surgery
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / blood*
  • Programmed Cell Death 1 Receptor / metabolism
  • Up-Regulation*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor