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

作者：Xin Xie, Jingdi Bai, Yu‐Hui Peng, Pingping Chen, Zhuxue Zhang, Daogui Fan, Feng Zhou, Yuan Yuan, Jiyun Liu, Yu Zhou, Hong Qin, Jianjun Hu, Juanjuan Duan, Wenli Fu, Ting Zhang, Hongmei Zeng, Jie Deng, Yang‐Ting Dong, Ying Liu, Xiaolan Qi, Wei Hong, Yan He, Chunlin Zhang, Wenfeng Yu, Qintian Yang, Yi Wei, Hua Bai, Qifang Zhang · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-19169-2 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune cells in cancer、Immune Cell Function and Interaction

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 promoted interleukin-1 receptor-associated kinase 2(IRAK2) transcription. IRAK2 overexpression rescued the effect of silencing STAT3-mediated cell viability, proliferation, migration and invasion. Additionally, IRAK2 facilitated interleukin-6 (IL6) expression via activating nuclear factor kappa-B (NFκB). Our results indicate that PD-L1/GP130/JAK2/STAT3/IRAK2/NFκB/IL6 axis promotes GBM cell viability, proliferation, migration and invasion via interacting with GP130 and PD-1 in GBM cells. Additionally, STAT3 transcriptionally promoted PD-L1 expression, thus forming loops to lead to PD-L1 autoregulation. IL6 positively correlated with GBM-associated macrophages, myeloid-derived suppressor cells...