CXCR4 has a unique ligand known as CXCL12 (also known as stromal-derived factor-1 or SDF-1), which is secreted from multiple stromal components in the TME, such as cancer-associated fibroblasts (CAFs), mesenchymal stem cells and endothelial cells (Figure 4) [57]. The gene discussed is CXCL12; the disease is cancer.