PD-L1 autoregulation promotes the proliferation, migration and invasion of glioblastoma cells via GP130/JAK2/STAT3/IRAK2/IL6 signaling pathway.

ABSTRACT: Glioblastoma (GBM) cells mediate immunosuppressive microenvironment, leading to poor response to programmed death-ligand 1(PD-L1) inhibitor therapy. How PD-L1 in GBM cells confers to GBM immunosuppressive microenvironment remains unclear. Here, we demonstrate that PD-L1 activated GP130/JAK2/STAT3/IRAK2/NFκB/IL6 pathway. We showed that PD-L1 was elevated in human primary GBM and promoted GBM cell viability, migration and invasion via activating janus kinase 2(JAK2) by interacting with glycoprotein 130(GP130) and PD-1 in GBM cells, leading to the activation of signal transducer and activator of transcription 3 (STAT3), a master that renders GBM immunosuppression. Overexpressing STAT3 reversed the effect of silencing PD-L1-mediated cell viability, proliferation, migration and invasion. STAT3

SUBMITTER: Xie X 

PROVIDER: S-EPMC12508128 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature