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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment
Brent A Hanks1, Alisha Holtzhausen, Katherine S Evans
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27708, USA.
The Journal of Clinical Investigation
|August 9, 2013
Summary
Tumor cells lacking Type III TGF-β receptor (TGFBR3) promote immune suppression by altering dendritic cell (DC) function, hindering anti-cancer immunity. Restoring TGFBR3 or using TGF-β inhibitors may improve immunotherapy effectiveness.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cancers employ immune evasion strategies, including manipulating dendritic cells (DCs) and regulatory T cells (Tregs), to promote progression and resist immunotherapy.
- Type III TGF-β receptor (TGFBR3) and its shed form (sTGFBR3) are crucial for epithelial homeostasis, and their loss is linked to breast cancer progression.
Purpose of the Study:
- To elucidate the mechanisms by which tumors manipulate DC and Treg function in the tumor microenvironment.
- To investigate the role of TGFBR3/sTGFBR3 loss in tumor immunoevasion and its impact on anti-tumor immunity.
Main Methods:
- Utilized murine models of breast cancer and melanoma.
- Analyzed TGF-β signaling, DC populations (plasmacytoid and myeloid), indoleamine 2,3-dioxygenase (IDO), and CCL22 chemokine expression.
- Assessed Treg infiltration and its effect on anti-tumor immunity.
Main Results:
- Loss of tumor-expressed TGFBR3/sTGFBR3 enhanced TGF-β signaling in locoregional DCs.
- This led to upregulated IDO in plasmacytoid DCs and CCL22 in myeloid DCs.
- These DC alterations promoted Treg infiltration and suppressed anti-tumor immunity.
Conclusions:
- Tumor TGFBR3/sTGFBR3 loss drives immune suppression via DC manipulation, contributing to cancer progression.
- TGF-β inhibitors could enhance immunotherapy efficacy.
- sTGFBR3 levels may serve as a predictive biomarker for immunotherapy response.
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