PD-L1 regulation by SDH5 via β-catenin/ZEB1 signaling

• Main Authors: Zhan Tuo, Yan Zong, Jie Li, Guangqin Xiao, Furong Zhang, Guiling Li, Sihua Wang, Yi Lv, Jiahong Xia, Jun Liu
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-12-01
• Series: OncoImmunology
• Subjects: lung cancer; pd-l1; sdh5; emt; immunotherapy
• Online Access: http://dx.doi.org/10.1080/2162402X.2019.1655361

Programmed death-ligand 1 (PD-L1) is a crucial target for lung cancer immunotherapy. In lung cancer patients with high PD-L1 expression, blocking or reducing its expression can inhibit tumor growth. PD-L1 is regulated by signaling pathways, transcription factors and epigenetic factors, such as the GSK3β/β-catenin pathway, P53 protein and EMT. In our previous study, succinate dehydrogenase 5 (SDH5) was reported to regulate ZEB1 expression, induce EMT and lead to lung cancer metastasis via the GSK3β/β-catenin pathway. It is possible that SDH5 is involved in the mechanisms of PD-L1 regulation.In the present study, we observed a negative correlation between the expression of PD-L1 and SDH5 in vivo and in vitro. The examination of patient tissues also confirmed our results. Furthermore, we also found that SDH5 could reverse PD-L1 expression by the GSK3β/β-catenin/ZEB1 pathways. All these results reveal that SDH5 regulates PD-L1 expression and suggest that SDH5 can be used as a marker to predict tumor immune micro-states and provide guidance for clinical immunotherapy.