We had shown previously that the ROS-producing enzyme NADPH oxidase-4 (NOX4) regulates myofibroblastic CAF differentiation in multiple cancers,4 and that NOX4 inhibition can revert myofibroblastic CAFs to a quiescent, fibroblast-like phenotype.3,4 Therefore, we examined whether targeting this pathway, using a small-molecule NOX4/1 inhibitor (GKT137831 [Setanaxib], Genyotex), could overcome CAF-mediated immunotherapy resistance. Here, NOX4 is linked to cancer.