The possible regulatory effect of the PD-1/PD-L1 signaling pathway on Tregs in ovarian cancer.
Gen Physiol Biophys
; 39(4): 319-330, 2020 Jul.
Article
en En
| MEDLINE
| ID: mdl-32902402
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-ß, and TGF-ß+ 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-ß+ anti-PD-L1 group showed a substantial decline in the differentiation of T-cells into Tregs compared with the TGF-ß group. Moreover, mice in the anti-PD-L1 group had significantly reduced tumor growth rates, Treg proportions in the tumor microenvironment, and FOXP3 expression.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Transducción de Señal
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Linfocitos T Reguladores
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Antígeno B7-H1
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Receptor de Muerte Celular Programada 1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article