3 years ago

E3 ubiquitin ligases Cbl-b and c-Cbl downregulate PD-L1 in EGFR wild-type non-small cell lung cancer

Lu Xu, Yibo Fan, Kezuo Hou, Ce Li, Ti Wen, Yunpeng Liu, Xiujuan Qu, Shuo Wang, Xiaofang Che, Ling Xu
Anti-PD-1/PD-L1 therapies have demonstrated prominent clinical effects in the treatment of non-small cell lung cancer (NSCLC). However, limited understanding of the regulatory mechanisms of PD-L1 has become one of the biggest challenges for further improving efficacy. In this study, we observed that in wild-type EFGR cell lines A549 and H460, the ubiquitin ligases Cbl-b and c-Cbl inhibit PD-L1 by inactivating STAT, AKT, and ERK signaling. MiR-181a and miR-940 were screened and validated to target Cbl-b and c-Cbl, respectively. Furthermore, in NSCLC tissues, the expression of Cbl-b/c-Cbl is negatively correlated with PD-L1 expression. Taken together, these findings indicated a new regulatory mechanism for PD-L1 in wild-type EGFR NSCLC cell lines by Cbl-b and c-Cbl. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/1873-3468.12985

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