Mechanistically, TGF-β/SMAD signaling in cancer-associated fibroblasts (CAFs) induces contractile myofibroblastic states and upregulates matrix constituents and modulators—collagens, fibronectin, versican, thrombospondins, latent TGF-β–binding proteins—together with crosslinking and alignment programs that increase stiffness and reduce interstitial porosity, thereby constraining lymphocyte trafficking (47–49). Here, FN1 is linked to cancer.