ACTA1 and neoplasm: Other contributing factors may be the secretion of various chemokines, cytokines, and proteases by CAFs, including transforming growth factor β, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, which promotes a fibrogenic milieu and potentiates local spread and distant metastases.27,28 As mesenchymal pathways are likely to be most active at the tumor periphery, it is intuitive that the expression of α-SMA in this compartment in pMMR tumors was found to be correlated with survival in the current study.