Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Ayano Kudo, Shintaro Kamo, Akinori Yamauchi, Sho Yoshimoto, Yuma Harada, Eiichi Kanai, Satoshi Takagi
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Subjects:
Cancer-associated fibroblasts
Tumor microenvironment
Dog
C-X-C motif chemokine ligand 12
C-X-C chemokine receptor 4
Transforming growth factor-β1
Online Access:https://doi.org/10.1038/s41598-025-16312-x
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322

Similar Items