Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1.

ABSTRACT: The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are the most prominent component of the breast cancer microenvironment because they influence tumor progression and the response to therapies. Here we show that macrophages acquire an immunosuppressive phenotype and increase the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species (ROS) inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine (BSO), and paclitaxel. Mechanistically, these agents cause accumulation of ROS that in turn activate NF-κB signaling to promote PD-L1 transcription and the release of immunosuppress

SUBMITTER: Roux C 

PROVIDER: S-EPMC6410837 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature