CXCL12, a member of the CXC family of chemokines, is secreted by the activated fibroblasts (for which we use the terms aPSCs and CAFs interchangeably in this review) of the TME and is a crucial mediator reported to contribute to growth and metastasis in PDAC and several other solid tumors, including head and neck squamous cell carcinoma (HNSCC) and breast, ovarian, and colorectal carcinomas [9,10,11]. The gene discussed is CXCL12; the disease is head and neck squamous cell carcinoma.