Central to this ecology, TGF-β and SMAD signaling from fibroblasts, myeloid cells, and tumor epithelium drives ECM deposition, angiogenesis, and cytotoxic T-cell exclusion, while in colon cancer models, TGF-β blockade converts “cold”, excluded tumors into checkpoint-responsive lesions [23,24]. This evidence concerns the gene TGFB1 and malignant colon neoplasm.