CMS4 tumors, characterized by high cancer associated fibroblast (CAF) and macrophage infiltration and lack of T- and NK-cell-mediated response, high epithelial-mesenchymal transition (EMT), TGF-β-associated signatures, and extracellular matrix (ECM) remodeling, have the worst prognosis and a poor response to anti-EGFR drugs and first-line chemotherapy regimens. Here, TGFB1 is linked to cancer.