ROS1-fusion protein induces PD-L1 expression via MEK-ERK activation in non-small cell lung cancer.

Journal Article (Journal Article)

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: The expression of PD-L1 in 30 primary NSCLC tumors with/without ROS1-fusion protein was evaluated by immunohistochemical (IHC) analysis. To assess the correlation between ROS1 fusion and PD-L1 expression, we down-regulated ROS1 with RNA interference or specific inhibitor (Crizotinib) in ROS1-fusion positive NSCLC cell line HCC78; or up-regulate ROS1-fusion gene in an immortalized human bronchial epithelial cell line (HBE). Mouse xenograft models were also used to determine the effect of ROS1 expression on PD-L1 expression in vivo. 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: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.

Full Text

Duke Authors

Cited Authors

  • Liu, Z; Zhao, K; Wei, S; Liu, C; Zhou, J; Gou, Q; Wu, X; Yang, Z; Yang, Y; Peng, Y; Cheng, Q; Liu, L

Published Date

  • May 6, 2020

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 1758003 -

PubMed ID

  • 32923114

Pubmed Central ID

  • 32923114

International Standard Serial Number (ISSN)

  • 2162-4011

Digital Object Identifier (DOI)

  • 10.1080/2162402X.2020.1758003

Language

  • eng

Conference Location

  • United States