Modulation of B cells and homing marker on NK cells through extracorporeal photopheresis in patients with steroid-refractory/resistant graft-vs.-host disease without hampering anti-viral/anti-leukemic effects
Graft-versus-host disease (GvHD), a severe complication of allogeneic hematopoietic stem cell transplantation, significantly affects the post-transplant morbidity and mortality. Systemic steroids remain the gold standard for the initial management of GvHD. However, up to 60% of patients will not suf...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
08 October 2018
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| In: |
Frontiers in immunology
Year: 2018, Volume: 9 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02207 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fimmu.2018.02207 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2018.02207/full 
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| Author Notes: | Lei Wang, Ming Ni, Angela Hückelhoven-Krauss, Leopold Sellner, Jean-Marc Hoffmann, Brigitte Neuber, Thomas Luft, Ute Hegenbart, Stefan Schönland, Christian Kleist, Martin Sill, Bao-an Chen, Patrick Wuchter, Volker Eckstein, William Krüger, Inken Hilgendorf, Ronit Yerushalmi, Arnon Nagler, Carsten Müller-Tidow, Anthony D. Ho, Peter Dreger, Michael Schmitt and Anita Schmitt |
| Summary: | Graft-versus-host disease (GvHD), a severe complication of allogeneic hematopoietic stem cell transplantation, significantly affects the post-transplant morbidity and mortality. Systemic steroids remain the gold standard for the initial management of GvHD. However, up to 60% of patients will not sufficiently respond to steroids. Extracorporeal photopheresis (ECP), a cell-based immunotherapy, has shown good clinical results in such steroid-refractory/resistant GvHD patients. Given its immunomodulatory, but not global immunosuppressive and steroid-sparing capacity, ECP constitutes an attractive option. In the case of GvHD, the balance of immune cells is destroyed: effector cells are not any longer efficiently controlled by regulatory cells. ECP therapy may restore this balance. However, the precise mechanism and the impact of ECP on anti-viral/anti-leukemic function remain unclear. In this study, 839 ECP treatments were performed on patients with acute GvHD (aGvHD) and chronic GvHD (cGvHD). A comprehensive analysis of effector and regulatory cells in patients under ECP therapy included multi-parametric flow cytometry and tetramer staining, LuminexTM-based cytokine, interferon-γ enzyme-linked immunospot and chromium-51 release assays. Gene profiling of myeloid-derived suppressor cells (MDSCs) was performed by microarray analysis. Immunologically, modulations of effector and regulatory cells as well as proinflammatory cytokines were observed under ECP treatment: (1) GvHD-relevant cell subsets like CD62L+ NK cells and newly defined CD19hiCD20hi B cells were modulated, but (2) quantity and quality of anti-viral/anti-leukemic effector cells were preserved. (3) The development of MDSCs was promoted and switched from an inactivated subset (CD33-CD11b+) to an activated subset (CD33+CD11b+). (4) The frequency of Foxp3+CD4+ regulatory T cells (Tregs) and CD24+CD38hi regulatory B cells was considerably increased in aGvHD patients, and Foxp3+CD8+ Tregs in cGvHD patients. (5) Proinflammatory cytokines like IL-1β, IL-6, IL-8 and TNF-α were significantly reduced. In summary, ECP constitutes an effective immunomodulatory therapy for patients with steroid-refractory/resistant GvHD without impairment of anti-viral/leukemia effects. |
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| Item Description: | Gesehen am 11.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02207 |