1. Academic Validation
  2. Expression of Programmed Death Ligand 1 Is Associated with the Prognosis of Intrahepatic Cholangiocarcinoma

Expression of Programmed Death Ligand 1 Is Associated with the Prognosis of Intrahepatic Cholangiocarcinoma

  • Dig Dis Sci. 2020 Feb;65(2):480-488. doi: 10.1007/s10620-019-05787-0.
Zhitao Dong 1 Boyi Liao 1 Weifeng Shen 1 Chengjun Sui 1 Jiamei Yang 2
Affiliations

Affiliations

  • 1 Department of Special Medical Care, Shanghai Eastern Hepatobiliary Surgery Hospital, The 13th Floor, No. 700 North Moyu Road, Jiading District, Shanghai, 200438, China.
  • 2 Department of Special Medical Care, Shanghai Eastern Hepatobiliary Surgery Hospital, The 13th Floor, No. 700 North Moyu Road, Jiading District, Shanghai, 200438, China. [email protected].
Abstract

Background: Programmed death ligand 1 (PD-L1) is expressed in many malignancies and plays a critical role in escape from immune surveillance through inhibition of its receptor programmed death 1. The role of PD-L1 in intrahepatic cholangiocarcinoma (ICC) and mechanisms of its regulation, however, remain largely unknown.

Aims: To analyze the expression and prognostic significance of PD-L1 in ICC and to study the regulatory mechanisms of PD-L1.

Methods: Samples were obtained from 125 patients diagnosed with ICC in the Eastern Hepatobiliary Surgery Hospital from January 2012 to January 2013. The records of each patient were analyzed to examine the relationship between PD-L1 and clinical data. In vitro experiments were performed to investigate the relationship between PD-L1 and the IL-6/mTOR signaling pathway and the feedback mechanism pathway of PD-L1.

Results: Expression of PD-L1 is closely related to tumor vascular invasion, lymphatic metastasis and TNM staging. High PD-L1 expression is closely related to poor prognosis in ICC. Mechanically, IL-6 induces PD-L1 expression through mTOR signaling in ICC cells. In addition, PD-L1 has a negative feedback inhibition effect on Akt signaling.

Conclusions: In summary, high PD-L1 expression was found to be associated with poor prognosis. The IL-6/mTOR pathway upregulates expression of PD-L1, thus promoting tumor invasion, and PD-L1 negatively inhibits the Akt pathway.

Keywords

B7-H1 antigen/CD274 protein, human; Cholangiocarcinoma, bile duct; Liver neoplasm; Prognosis; Signal transduction.

Figures
Products