CXCL12 and neoplasm: TGF-β signaling in the TME also promotes macrophage M2 polarization, and TGF-beta activates fibroblasts to form CAFs that secrete a higher level of CXCL12, which binds to the cognate receptor CXCR4 on M2 macrophages, leading to tumor cell growth (Wu et al., 2022).