IFN-γ induces PD-L1 through p38/JNK/ERK signaling pathways and counteracts the tumor promoting effect mediated by PD-L1 in Glioblastoma

• Published in: Computational intelligence and neuroscience Vol. 2022; pp. 5492602 - 9
• Main Authors: Jia, Huafang, Xie, Xiaoli, Wang, Long, Wang, Lijuan, Che, Fengyuan
• Format: Journal Article
• Language: English
• Published: United States Hindawi 29.06.2022; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Antibodies; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biological response modifiers; Brain cancer; Brain tumors; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Chemotherapy; Clinical trials; Extracellular signal-regulated kinase; Flow cytometry; Gelatinase A; Glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Glioblastoma cells; Glioblastoma multiforme; Glioma; Humans; Inflammation; Interferon; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Medical research; Molecular biology; Motility; PD-L1 protein; Proteins; Radiation therapy; RNA; Signal Transduction; Signaling; Software; Tumors; Vimentin; Wound healing; γ-Interferon; China; United States > US
• ISSN: 1687-5265; 1687-5273
• DOI: 10.1155/2022/5492602

Glioblastoma is the most malignant primary glioma. Conventional treatment methods that include surgery, radiotherapy, and chemotherapy have a limited curative effect on the tumor. With the deepening of molecular biology research, molecular targeted therapy has opened a new era of tumor therapy. Programmed death ligand 1 (PD-L1) has been proved to play a pivotal role in the tumor immune evasion process. Previous studies have confirmed the specific expression of PD-L1 in glioblastoma tissues and cells, but there are few studies on inflammation regulating PD-L1 in glioblastoma. In this study, real-time PCR, flow cytometry, and western blot were applied to detect PD-L1 in glioblastoma cells. Short hairpin RNA was used to knock down PD-L1 in glioblastoma cells. Cell counting kit-8 experiment and wound-healing assay were used to detect the proliferation and migration of glioblastoma cells. Here we demonstrated that PD-L1 was overexpressed in glioblastoma cells, and interferon-gamma (IFN-γ) induces PD-L1 in glioblastoma cells via activating p38/JNK/ERK signaling pathways. To summarize, PD-L1 promotes the occurrence and development of glioblastoma. IFN-γ counteracts the tumor-promoting effects mediated by PD-L1 in glioblastoma. IFN-γ regulates PD-L1 through multiple signaling pathways, but the total effect of IFN-γ-mediated inflammatory signals still need to be further explored in glioblastoma. PD-L1 enhances the proliferation and migration of glioblastoma cells by regulating CDK4, CDK6, MMP-2, and vimentin molecules. Most importantly, targeting PD-L1 can be applied in the treatment of glioblastoma. We speculate that IFN-γ may affect glioblastoma through other pathways, and we will continue to further explore the mechanisms in the future.