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

Abstract

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.