Regulatory T Cells Induce Metastasis by Increasing Tgf-β and Enhancing the Epithelial–Mesenchymal Transition

Area of Science:

• Immunology
• Oncology
• Cancer Metastasis

Background:

• Malignant melanoma is an aggressive skin cancer with frequent distant metastases.
• The precise mechanisms driving melanoma metastasis remain incompletely understood.
• Regulatory T cells (Tregs) play a role in immune suppression within the tumor microenvironment.

Purpose of the Study:

• To investigate the role of exogenous regulatory T cells (Tregs) in promoting melanoma metastasis.
• To elucidate the cellular and molecular mechanisms by which Tregs influence melanoma cell invasiveness and migration.

Main Methods:

• Administration of exogenous Tregs to melanoma tumor-bearing mice (B16-BL6 model).
• Assessment of lung metastasis following Treg administration.
• Analysis of melanoma cell phenotype, including invasive and migratory capacity.
• Measurement of transforming growth factor-β (TGF-β) expression and epithelial-to-mesenchymal transition (EMT) markers.
• Evaluation of endogenous Treg recruitment into tumor tissues.

Main Results:

• Exogenous Treg administration significantly increased lung metastasis in melanoma-bearing mice.
• Cell-to-cell contact between melanoma cells and Tregs elevated TGF-β expression and induced EMT in melanoma cells.
• Co-culture with Tregs enhanced melanoma cell migration, and Treg injection promoted endogenous Treg infiltration into tumors.

Conclusions:

• Exogenous Tregs promote melanoma metastasis by enhancing cell invasiveness and migration.
• Treg-mediated upregulation of TGF-β and induction of EMT are key mechanisms driving melanoma metastasis.
• These findings highlight a novel role for Tregs in augmenting melanoma's metastatic potential.