Targeting GARP:TGF-β1 complexes on Tregs for the immunotherapy of myeloproliferative neoplasms
(2022)
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- Authors
- Supervisors
- Lucas, Sophie
- Abstract
- BCR-ABL negative myeloproliferative neoplasms (MPN) form a group of rare hematological malignancies. Most severe form associates aberrant production of inflammatory cytokines with bone marrow fibrosis and extramedullary hematopoiesis. TGF-β1, a potent pro-fibrotic and immunosuppressive cytokine, plays a major role here. However, the cell type that activates TGF-β1 in MPN remains unknown. Our work reveals the involvement of GARP-expressing regulatory T cells (Treg) in mouse models of MPN. GARP is a transmembrane protein expressed on the surface of Tregs that binds and activates TGF-β1. Selective blocking of TGF-β1 activation by Tregs with anti-GARP:TGF-β1 antibodies decreases tumor burden in murine MPN. The mechanism of action involves cytotoxic T lymphocytes, suggesting an action on the anti-tumor immune response. Anti-GARP:TGF-β1 antibodies could therefore be a promising immunotherapy in MPN.
- Affiliations
Citations
Devreux, J. (2022). Targeting GARP:TGF-β1 complexes on Tregs for the immunotherapy of myeloproliferative neoplasms. https://hdl.handle.net/2078.5/24917