Open Access

Liver kinase B1 in exosomes inhibits immune checkpoint programmed death ligand 1 and metastatic progression of intrahepatic cholangiocarcinoma

  • Authors:
    • Zhuo Liu
    • Kunyan Zhou
    • Jian Zeng
    • Xin Zhou
    • Huanyu Li
    • Ke Peng
    • Xiang Liu
    • Feng Li
    • Bin Jiang
    • Ming Zhao
    • Tiexiang Ma
  • View Affiliations

  • Published online on: July 15, 2022     https://doi.org/10.3892/or.2022.8367
  • Article Number: 155
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The increasing morbidity and high mortality of intrahepatic cholangiocarcinoma (ICC) has led to the urgent need for new diagnostics and therapeutics. Liver kinase B1 (LKB1) exerts a tumor suppressor role in multiple malignances, while its regulatory role in exosomes secreted by ICC cells is obscure. In the present study, exosomes were extracted from cell culture supernatants of RBE and HCCC‑9810 ICC cells as well as plasma of patients with ICC by ultracentrifugation and the morphology of exosomes was identified by transmission electron microscopy. Notably, compared with that of intracellular LKB1, the protein level of exosomal LKB1 was decreased. Silencing intracellular LKB1 increased the protein levels of programmed death ligand 1 (PD‑L1), Slug and phosphorylated‑AKT in exosomes, accompanied by decreased expression levels of exosomal LKB1. Exosomes with lower protein levels of LKB1 promoted the expression of the immune checkpoint PD‑L1, malignant phenotypes of ICC cells in vitro, and cancer metastasis in vivo. Moreover, the low level of exosomal LKB1 in plasma was tightly associated with the poor prognosis of patients with ICC. Collectively, exosomal LKB1 inhibits the immune checkpoint PD‑L1 and metastasis of ICC cells. These findings may provide new methods for the diagnosis and immune therapy of ICC.

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September-2022
Volume 48 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu Z, Zhou K, Zeng J, Zhou X, Li H, Peng K, Liu X, Li F, Jiang B, Zhao M, Zhao M, et al: Liver kinase B1 in exosomes inhibits immune checkpoint programmed death ligand 1 and metastatic progression of intrahepatic cholangiocarcinoma. Oncol Rep 48: 155, 2022
APA
Liu, Z., Zhou, K., Zeng, J., Zhou, X., Li, H., Peng, K. ... Ma, T. (2022). Liver kinase B1 in exosomes inhibits immune checkpoint programmed death ligand 1 and metastatic progression of intrahepatic cholangiocarcinoma. Oncology Reports, 48, 155. https://doi.org/10.3892/or.2022.8367
MLA
Liu, Z., Zhou, K., Zeng, J., Zhou, X., Li, H., Peng, K., Liu, X., Li, F., Jiang, B., Zhao, M., Ma, T."Liver kinase B1 in exosomes inhibits immune checkpoint programmed death ligand 1 and metastatic progression of intrahepatic cholangiocarcinoma". Oncology Reports 48.3 (2022): 155.
Chicago
Liu, Z., Zhou, K., Zeng, J., Zhou, X., Li, H., Peng, K., Liu, X., Li, F., Jiang, B., Zhao, M., Ma, T."Liver kinase B1 in exosomes inhibits immune checkpoint programmed death ligand 1 and metastatic progression of intrahepatic cholangiocarcinoma". Oncology Reports 48, no. 3 (2022): 155. https://doi.org/10.3892/or.2022.8367