Platelet-Derived GARP Induces Peripheral Regulatory T Cells-Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis.
Niklas ZimmerFranziska K KrebsSophia ZimmerHeidrun Mitzel-RinkElena J KummKerstin JurkStephan GrabbeCarmen LoquaiAndrea TuettenbergPublished in: Cancers (2020)
Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet-T cell interaction in immune-mediated diseases remains limited. Glycoprotein A repetitions predominant (GARP) expressed on platelets and on activated regulatory T cells (Treg) is involved in the regulation of peripheral immune responses by modulating the bioavailability of transforming growth factor β (TGF-β). Soluble GARP (sGARP) exhibits strong regulatory and anti-inflammatory capacities both in vitro and in vivo, leading to the induction of peripheral Treg. Herein, we investigated the effect of platelet-derived GARP on the differentiation, phenotype, and function of T effector cells. CD4+CD25- T cells cocultured with platelets upregulated FoxP3, the master transcription factor for Treg, were anergic, and were strongly suppressive. These effects were reversed by using a blocking anti-GARP antibody, indicating a dependency on GARP. Importantly, melanoma patients in different stages of disease showed a significant upregulation of GARP on the platelet surface, correlating to a reduced responsiveness to immunotherapy. In conclusion, our data indicate that platelets induce peripheral Treg via GARP. These findings might contribute to diseases such as cancer-associated thrombocytosis, wherein poor prognosis and metastasis are associated with high counts of circulating platelets.
Keyphrases
- regulatory t cells
- poor prognosis
- transforming growth factor
- dendritic cells
- immune response
- transcription factor
- end stage renal disease
- long non coding rna
- epithelial mesenchymal transition
- anti inflammatory
- signaling pathway
- cell proliferation
- healthcare
- mass spectrometry
- risk assessment
- toll like receptor
- peritoneal dialysis
- social media
- cell death
- electronic health record
- oxidative stress
- peripheral blood
- patient reported
- skin cancer
- atomic force microscopy
- climate change
- basal cell carcinoma