Home FOR AUTHORS General Physiology and Biophysics 2020 General Physiology and Biophysics Vol.39, No.4, p.319–330, 2020

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Founded: 1982
ISSN  1338-4325 (online)

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General Physiology and Biophysics Vol.39, No.4, p.319–330, 2020

Title: The possible regulatory effect of the PD-1/PD-L1 signaling pathway on Tregs in ovarian cancer
Author: Jian-Xia Chen, Xi-Juan Yi, Shan-Xia Gao, Jin-Xia Sun
Abstract: Aim of this study was to investigate the possible regulatory effect of the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway on Tregs in ovarian cancer. Immunohistochemistry was used to detect the expression of PD-L1 and PD-1 and the presence of FOXP3+ Tregs in ovarian cancer. Then, ovarian cancer HO8910 cells were subjected to transfection with PD-L1 siRNA in vitro. CCK-8, Transwell and wound healing assays were performed to detect the biological behaviors of ovarian cancer cells. Human T-cells isolated from human peripheral blood were cocultured with HO8910 cells, which were divided into the Control, TGF-β, and TGF-β+ anti-PD-L1 groups. The proportion of differentiated Tregs was detected by flow cytometry. Mouse models of ovarian cancer were established, and PD-L1 antibody therapy was administered. Tumor growth and Treg recruitment were observed. PD-L1, PD-1 and FOXP3+ Tregs were found in ovarian cancer tissue. Patients with tumors with an advanced stage and low differentiation and lymph node metastasis had significantly higher levels of PD-1, PD-L1 and FOXP3+ Tregs. After transfection with PD-L1 siRNA, HO8910 cells showed a significant reduction in PD-L1 expression, proliferation, migration and invasion. After T-cells were cocultured with ovarian cancer cells, the TGF-β+ anti-PD-L1 group showed a substantial decline in the differentiation of T-cells into Tregs compared with the TGF-β group. Moreover, mice in the anti-PD-L1 group had significantly reduced tumor growth rates, Treg proportions in the tumor microenvironment, and FOXP3 expression.
Keywords: Ovarian cancer — PD-1 — PD-L1 — Tregs — Tumor immune escape
Published online: 17-Aug-2020
Year: 2020, Volume: 39, Issue: 4 Page From: 319, Page To: 330
doi:10.4149/gpb_2020011


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