Open AccessThe possible regulatory effect of the PD-1/PD-L1 signaling pathway on Tregs in ovarian cancer
Author(s) -
Jianxia Chen,
Xi-Juan Yi,
Gao Shan-xia,
Jie Sun
Publication year - 2020
Publication title -
general physiology and biophysics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.376
H-Index - 39
eISSN - 1338-4325
pISSN - 0231-5882
DOI - 10.4149/gpb_2020011
Subject(s) - foxp3 , ovarian cancer , cancer research , pd l1 , flow cytometry , tumor microenvironment , cancer , metastasis , medicine , immunology , immune system , immunotherapy
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.