ROS1-fusion protein induces PD-L1 expression via MEK-ERK activation in non-small cell lung cancer
Zheng Liu, Kejia Zhao, Shiyou Wei, Chengwu Liu, Jiankang Zhou, Qiheng Gou, Xia Wu, Zhenyu Yang, Yanbo Yang, Yong Peng, Qing Cheng, Lunxu Liu
Abstract
Introduction: Despite some of the oncogenic driver mutations that have been associated with increased expression of programmed death-ligand 1 (PD-L1), the correlation between PD-L1 expression and ROS1 fusion in NSCLC cells, especially for those with Crizotinib resistance has not been fully addressed. Materials and Methods: . Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression. Results: ROS1-rearrangement in primary NSCLC tumor was significantly associated with up-regulated PD-L1 expression. PD-L1 expression was significantly up-regulated in bronchial epithelial cells after forced expression of ROS1 fusion and was eliminated when HCC78 xenograft mouse models were treated with Crizotinib. We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion. Conclusions: rearrangement.