Highlights
- •ECP was able to increase Tfh cells to ameliorate GvHD.
- •Upregulation of Th22 cells was observed in aGvHD patients with CR.
- •Tim-3 expression was downregulated on effector T cells by ECP.
- •ECP shows immunomodulatory effects in GvHD setting.
Abstract
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.
Keywords
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Article info
Publication history
Published online: October 25, 2021
Accepted:
September 13,
2021
Received:
August 5,
2021
Identification
Copyright
© 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
