Remarkably, CAFs can also remodel the ECM to create a physical barrier to infiltrating immune cells [291,292], and analysis of TCGA RNA-seq data from 15 different tumor types has revealed that deregulation of ECM-related genes in CAFs correlates with increased TGFβ signaling and insensitivity to ICB [251], suggesting that CAF coordinated creation of a reactive stromal TME, via ECM remodeling and TGFβ signaling, contributes to the development of a cold immune microenvironment in the prostate, thus rendering ICB ineffective. This evidence concerns the gene TGFB1 and neoplasm.