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

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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.

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Acknowledgments

The authors thank Dr. Binghua Dai and Dr. Jiongjiong Lu for secretarial work.

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Authors and 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

    Zhitao Dong, Boyi Liao, Weifeng Shen, Chengjun Sui & Jiamei Yang

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  1. Zhitao Dong
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Contributions

ZD, BL: Conception and design, Development of methodology. CS, WS: Analysis and interpretation of data (e.g., statistical analysis). ZD: Writing, review, and/or revision of the manuscript. CS, WS: Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases).

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Correspondence to Jiamei Yang.

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Dong, Z., Liao, B., Shen, W. et al. Expression of Programmed Death Ligand 1 Is Associated with the Prognosis of Intrahepatic Cholangiocarcinoma. Dig Dis Sci 65, 480–488 (2020). https://doi.org/10.1007/s10620-019-05787-0

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  • DOI: https://doi.org/10.1007/s10620-019-05787-0

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