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

Medientyp: E-Artikel

Titel: 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

Beteiligte: Wang, Lei [VerfasserIn]; Ni, Ming [VerfasserIn]; Hückelhoven-Krauss, Angela [VerfasserIn]; Sellner, Leopold [VerfasserIn]; Hoffmann, Jean-Marc [VerfasserIn]; Neuber, Brigitte [VerfasserIn]; Luft, Thomas [VerfasserIn]; Hegenbart, Ute [VerfasserIn]; Schönland, Stefan [VerfasserIn]; Kleist, Christian [VerfasserIn]; Sill, Martin [VerfasserIn]; Wuchter, Patrick [VerfasserIn]; Eckstein, Volker [VerfasserIn]; Müller-Tidow, Carsten [VerfasserIn]; Ho, Anthony Dick [VerfasserIn]; Dreger, Peter [VerfasserIn]; Schmitt, Michael [VerfasserIn]; Schmitt, Anita [VerfasserIn]

Erschienen: 08 October 2018

Sprache: Englisch

DOI: 10.3389/fimmu.2018.02207

ISSN: 1664-3224

Identifikator:

Schlagwörter: (1) GvHD ; (2) ECP ; (3) immunomodulation ; (4) regulatory cells ; (5) pro-inflammatory cytokines ; (6) effector cells ; (7) anti-viral effect ; (8) anti-leukemic effect

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Beschreibung: 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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