GARP-dependent TGF-β1 activation in myeloproliferative neoplasms : a new therapeutic target.
(2021)
Files
ThèseFINAL-SaraLecomte.pdf
Closed Access - Adobe PDF
- 99.66 MB
Details
- Authors
- Supervisors
- Lucas, Sophie
- Abstract
- Myeloproliferative neoplasms (MPNs) are a type of blood cancers characterized by abnormal hematopoiesis and, in the most severe cases, bone marrow fibrosis. Treatment options are limited. TGF-β1, a potent immunosuppressive and pro-fibrotic cytokine, is implicated in the pathogenesis of MPNs. However, how the active cytokine is produced in MPNs is unknow. Here, we found that GARP-expressing regulatory T cells (Tregs) are implicated in experimentally induced MPNs in mice. GARP is a transmembrane protein that binds and activates latent TGF-β1 on the Treg cell surface. Selectively blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 antibodies moderately reduced fibrosis, and importantly, it significantly reduced tumor burden in murine MPNs. The effect appears to involve the stimulation of anti-tumor immune responses. Thus, anti-GARP:TGF-β1 antibodies may serve as a novel approach for the treatment of patients suffering from MPNs.
- Affiliations
Citations
Lecomte, S. (2021). GARP-dependent TGF-β1 activation in myeloproliferative neoplasms : a new therapeutic target. https://hdl.handle.net/2078.5/114115