Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1
Abstract 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 recepto...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-16312-x |
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| author | Ayano Kudo Shintaro Kamo Akinori Yamauchi Sho Yoshimoto Yuma Harada Eiichi Kanai Satoshi Takagi |
| author_facet | Ayano Kudo Shintaro Kamo Akinori Yamauchi Sho Yoshimoto Yuma Harada Eiichi Kanai Satoshi Takagi |
| author_sort | Ayano Kudo |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2ea9bfc42a414ab68044f1e6cb454354 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-2ea9bfc42a414ab68044f1e6cb4543542025-08-24T11:24:22ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-16312-xExploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1Ayano Kudo0Shintaro Kamo1Akinori Yamauchi2Sho Yoshimoto3Yuma Harada4Eiichi Kanai5Satoshi Takagi6Laboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityLaboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu UniversityAbstract 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.https://doi.org/10.1038/s41598-025-16312-xCancer-associated fibroblastsTumor microenvironmentDogC-X-C motif chemokine ligand 12C-X-C chemokine receptor 4Transforming growth factor-β1 |
| spellingShingle | Ayano Kudo Shintaro Kamo Akinori Yamauchi Sho Yoshimoto Yuma Harada Eiichi Kanai Satoshi Takagi Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 Scientific Reports Cancer-associated fibroblasts Tumor microenvironment Dog C-X-C motif chemokine ligand 12 C-X-C chemokine receptor 4 Transforming growth factor-β1 |
| title | Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 |
| title_full | Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 |
| title_fullStr | Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 |
| title_full_unstemmed | Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 |
| title_short | Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1 |
| title_sort | exploring the effect of canine cancer associated fibroblasts on t cell dynamics through the cxcl12 cxcr4 axis modulated by tgf β1 |
| topic | Cancer-associated fibroblasts Tumor microenvironment Dog C-X-C motif chemokine ligand 12 C-X-C chemokine receptor 4 Transforming growth factor-β1 |
| url | https://doi.org/10.1038/s41598-025-16312-x |
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