Research Paper|Volume 16, Issue 14|pp 11373—11384

High expression of circulating exosomal PD-L1 contributes to immune escape of hepatocellular carcinoma and immune clearance of chronic hepatitis B

Xiaoqing Lin¹, Hui Shao², Yongzhi Tang², Qiupeng Wang², Zhenyu Yang², Hongwei Wu², Tongjing Xing²

¹Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, Wenzhou Sixth People’s Hospital, Wenzhou, Zhejiang, China
²Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China

Received: January 2, 2024Accepted: April 9, 2024Published: July 17, 2024

https://doi.org/10.18632/aging.206020

Copyright: © 2024 Xing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To investigate the expression of programmed death ligand-1 (PD-L1) in circulating exosomes, and to define the role of exosomal PD-L1 in promoting immune escape mechanism during chronic hepatitis B infection (CHB) and related liver diseases.

Methods: The levels of PD-L1 expressed in exosomes were detected by ELISA. CD8+T cells were sorted and cytotoxicity test was assessed by flow cytometry. PD-L1 protein expression in hepatocellular carcinoma (HCC) and normal adjacent tissues were detected by immunohistochemistry.

Results: Circulating exosomal PD-L1 levels were significantly higher in patients with CHB and HCC than in healthy controls (F =7.46, P=0.001). Levels of CD107a on CD8+T cells in patients with CHB receiving PD-L1 blocking antibody were significantly lower than in patients receiving isotype blocking antibody (t = 4.96, P < 0.01). Levels of TNF-α in cell culture supernatants of the PD-L1 blocking antibody group were significantly higher than in the isotype blocking antibody group (t =5.92, P < 0.01). Compared with patients receiving isotype blocking antibody, levels of CD107a on CD8+T cells significantly increased in patients with HCC receiving anti-PD-L1 antibody (t = 3.51, P<0.05). Compared with adjacent tissues, the levels of PD-L1 protein expression in HCC tissues were slightly higher; however, no significant difference between the two groups was observed.

Conclusions: PD-L1 blockade in exosomes might promote the cytotoxic function of CD8+T cells and inhibit immune evasion during progression of HCC. Blocking PD-L1 in exosomes reduced the cytotoxic function of CD8+T cells in patients with CHB while enhancing the production of proinflammatory cytokines.