Regulation of PD-L1 expression in K-ras-driven cancers through ROS-mediated FGFR1 signaling.

ABSTRACT: K-ras mutations are major genetic events that drive cancer development associated with aggressive malignant phenotypes, while expression of the immune checkpoint molecule PD-L1 plays a key role in cancer evasion of the immune surveillance that also profoundly affects the patient outcome. However, the relationship between K-ras oncogenic signal and PD-L1 expressions as an important area that requires further investigation. Using both in vitro and in vivo experimental models of K-ras-driven cancer, we found that oncogenic K-ras significantly enhanced PD-L1 expression through a redox-mediated mechanism. Activation of K-ras^G12V promoted ROS generation and induced FGFR1 expression, leading to a significant upregulation of PD-L1. We further showed that exogenous ROS such as hydrogen p

SUBMITTER: Glorieux C 

PROVIDER: S-EPMC7658718 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature