TGFB1 and cancer: Congruently, in the typical hypoxic TIME, increased TGF-β stimulates CXCL12/CXCR4 signaling via HIF-1α in both cancer cells and CAFs [263], and the elevation of CXCL12/CXCR4 axis serves the downstream role to recruit and activate CAFs, thereby driving matrix production and subsequent stromal T-lymphocyte exclusion [264].