The pleiotropic nature of CAFs can associate with both pro-inflammatory and anti-inflammatory gene signatures and the secretion of soluble signal mediators, e.g., TNF-α, IFN-γ, TGF-β, PGE2, IDO, CXCL-12/SDF1, CCL2/MCP-1, Tenascin-C, IL-6, IL-4, CXCL8 [17], and nitric oxide [44], that potentially affect macrophage polarization in different ways at different stages of cancer progression [44]. This evidence concerns the gene IL4 and cancer.