Response to extracorporeal photopheresis therapy of patients with steroid-refractory/-resistant GvHD is associated with up-regulation of Th22 cells and Tfh cells.
ECP
Fas-mediated apoptosis
GvHD
Th cells
immune checkpoint molecules
immunomodulation
Journal
Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
05
08
2021
revised:
09
09
2021
accepted:
13
09
2021
pubmed:
30
10
2021
medline:
26
4
2022
entrez:
29
10
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34711501
pii: S1465-3249(21)00822-7
doi: 10.1016/j.jcyt.2021.09.008
pii:
doi:
Substances chimiques
Hepatitis A Virus Cellular Receptor 2
0
Steroids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
311-319Informations de copyright
Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest The authors declare no competing financial interests, except the following: Funding was provided by Mallinckrodt to AS and MS for the documentation of the clinical course and for the analysis of patient immune cells; MS received funding for collaborative research from Apogenix, Hexal and Novartis and travel grants from Hexal and Kite; he received financial support for educational activities and conferences from bluebird bio, Kite and Novartis; he is a board member for MSD and (co-)PI of clinical trials of MSD, GSK, Kite and BMS. AS received travel grants from Hexal and Jazz Pharmaceuticals. MS and AS are co-founders and shareholders of TolerogenixX Ltd. AS and LW are part-time and full-time employees, respectively, of TolerogenixX Ltd.