biostudies-literatureKudo AJapan Society for the Promotion of Science (JSPS) KAKENHI31050https://www.ebi.ac.uk/biostudies/studies/S-EPMC12375069biostudies-literatureUnknown15(1)Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that modulate T cell immunity by secreting humoral factors and forming structural barriers. CAFs secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which binds to C-X-C chemokine receptor 4 (CXCR4) on T cells and induces chemotaxis. Transforming growth factor beta 1 (TGF-β1), another humoral factor secreted by CAFs, has been reported to regulate the CXCL12/CXCR4 axis; however, a direct association between them has not been demonstrated in human medicine or veterinary medicine. This study investigated the role of canine CAFs in T cell migration through the CXCL12/CXCR4 axis and the regulatory influence of TGF-β1. CXCL12 and CXCR4 were expressed in the tumor stroma and on T cells, respectively, in dogs with epithelial malignant tumors. Canine CAFs secreted higher levels of CXCL12 and TGF-β1 than normal fibroblasts, and CAF-derived TGF-β1 modulated both CXCL12 secretion by CAFs and CXCR4 expression on T cells. Furthermore, canine CAFs induced T cell migration through the CXCL12/CXCR4 axis. These findings indicate that CAFs may influence T cell migration through the CXCL12/CXCR4 axis under the regulation of TGF-β1 signaling, highlighting their potential role in shaping T cell dynamics within the TME.Scientific reportsExploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1.PMC12375069JP24KJ2120Kanai EYamauchi AHarada YTakagi SKudo AYoshimoto SKamo SfalseExploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1.Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that modulate T cell immunity by secreting humoral factors and forming structural barriers. CAFs secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which binds to C-X-C chemokine receptor 4 (CXCR4) on T cells and induces chemotaxis. Transforming growth factor beta 1 (TGF-β1), another humoral factor secreted by CAFs, has been reported to regulate the CXCL12/CXCR4 axis; however, a direct association between them has not been demonstrated in human medicine or veterinary medicine. This study investigated the role of canine CAFs in T cell migration through the CXCL12/CXCR4 axis and the regulatory influence of TGF-β1. CXCL12 and CXCR4 were expressed in the tumor stroma and on T cells, respectively, in dogs with epithelial malignant tumors. Canine CAFs secreted higher levels of CXCL12 and TGF-β1 than normal fibroblasts, and CAF-derived TGF-β1 modulated both CXCL12 secretion by CAFs and CXCR4 expression on T cells. Furthermore, canine CAFs induced T cell migration through the CXCL12/CXCR4 axis. These findings indicate that CAFs may influence T cell migration through the CXCL12/CXCR4 axis under the regulation of TGF-β1 signaling, highlighting their potential role in shaping T cell dynamics within the TME.2025-01-01T00:00:00Z2025 Aug2026-05-09T17:56:03.686Z2026-04-08T01:08:43.92ZS-EPMC123750694084950810.1038/s41598-025-16312-x