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Response to extracorporeal photopheresis therapy of patients with steroid-refractory/-resistant GvHD is associated with up-regulation of Th22 cells and Tfh cells

Extracorporeal photopheresis (ECP), a personalized cellular immunotherapy, constitutes a promising treatment for steroid-refractory/-resistant graft-versus-host disease (SR-GvHD), with encouraging clinical response rates. To further investigate its mechanism of action, ECP's effects on T helper...

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Main Authors: Ni, Ming (Author) , Wang, Lei (Author) , Ding, Yuntian (Author) , Gong, Wenjie (Author) , Wang, Sanmei (Author) , Neuber, Brigitte (Author) , Schubert, Maria-Luisa (Author) , Sauer, Tim (Author) , Hückelhoven-Krauss, Angela (Author) , Luft, Thomas (Author) , Hegenbart, Ute (Author) , Schönland, Stefan (Author) , Eckstein, Volker (Author) , Wang, Jishi (Author) , Krüger, William (Author) , Müller-Tidow, Carsten (Author) , Dreger, Peter (Author) , Schmitt, Michael (Author) , Schmitt, Anita (Author)
Format: Article (Journal)
Language:English
Published: March 2022
In: Cytotherapy
Year: 2022, Volume: 24, Issue: 3, Pages: 311-319
ISSN:1477-2566
DOI:10.1016/j.jcyt.2021.09.008
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jcyt.2021.09.008
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1465324921008227
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Author Notes:Ming Ni, Lei Wang, Yuntian Ding, Wenjie Gong, Sanmei Wang, Brigitte Neuber, Maria-Luisa Schubert, Tim Sauer, Angela Hückelhoven-Krauss, Thomas Luft, Ute Hegenbart, Stefan Schönland, Volker Eckstein, Jishi Wang, William Krüger, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt, Anita Schmitt
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Summary:Extracorporeal photopheresis (ECP), a personalized cellular immunotherapy, constitutes a promising treatment for steroid-refractory/-resistant graft-versus-host disease (SR-GvHD), with encouraging clinical response rates. To further investigate its mechanism of action, ECP's effects on T helper (Th) cells as well as on expression of immune checkpoint (PD-1 and Tim-3) and apoptotic (Fas receptor [FasR]) molecules were investigated in 27 patients with SR-GvHD. Our data show that GvHD patients had significantly higher levels of Th2, Th17, Th22 and granulocyte-macrophage colony-stimulating factor (GM-CSF)-positive Th (ThG) cells and clearly lower levels of T follicular helper (Tfh) cells, including Th1- and Th2-like cells, compared with healthy donors. ECP therapy for GvHD was effective through the modulation of different Th subsets: increases of Th22 (1.52-fold) and Tfh cells (1.48-fold) in acute GvHD (aGvHD) and increases of Th2-like Tfh cells (1.74-fold) in chronic GvHD (cGvHD) patients were associated with clinical response. Expression of FasR was further upregulated in CD4+CD8+ T cells. Additionally, Tim-3-expressing effector T cells associated with the severity of GvHD were reduced. Taken together, these data show that ECP therapy exerts immunomodulatory effects by promoting a balanced immune reconstitution and inducing immune tolerance. Therefore it represents an attractive option for the treatment of GvHD.
Item Description:Available online 25 October 2021
Gesehen am 08.06.2022
Physical Description:Online Resource
ISSN:1477-2566
DOI:10.1016/j.jcyt.2021.09.008

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