Efficiency of human monocyte-derived suppressor cell-based treatment in graft-versus-host disease prevention while preserving graft-versus-leukemia effect
Open Access
- 1 January 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in OncoImmunology
- Vol. 10 (1), 1880046
- https://doi.org/10.1080/2162402x.2021.1880046
Abstract
Immunosuppressive cell-based therapy is a recent strategy for controlling Graft-versus-Host Disease (GvHD). Such cells ought to maintain their suppressive function in inflammatory conditions and in the presence of immunosuppressive agents currently used in allogeneic hematopoietic cell transplantation (allo-HCT). Moreover, these therapies should not diminish the benefits of allo-HCT, the Graft-versus-Leukemia (GvL) effect. We have previously reported on a novel subset of human monocyte-derived suppressor cells (HuMoSC) as a prospective approach for controlling GvHD.Objective The objective of this study was to explore the therapeutic relevance of the HuMoSC in clinical conditions. Immune regulatory functions of HuMoSC were assessed in inflammatory conditions and in the presence of immunosuppressants. The therapeutic efficiency of the association of HuMoSC with immunosuppressants was evaluated in an experimental model of GvHD induced by human PBMC in NOD/SCID/IL2-Rγc−/− (NSG) mice. Interestingly, the inhibitory functions of HuMoSC against T lymphocytes and their ability to polarize Treg are preserved, in vitro, in inflammatory environments and are not affected by immunosuppressive agents. In vivo, the association of HuMoSC-based treatment with an immunosuppressive drug showed a synergistic effect for controlling GvHD. Furthermore, HuMoSC control GvHD while preserving GvL effect in a xeno-GvHD conditioned mouse model with cell neoplasm (CAL-1). HuMoSC are generated according to good manufacturing practices (GMP) and we demonstrated that these cells tolerate long-term preservation with unaltered phenotype and function.Conclusion HuMoSC-based therapy represents a promising approach for controlling GvHD and could be quickly implemented in clinical practice.Keywords
Funding Information
- Région Bourgogne Franche-Comté
This publication has 31 references indexed in Scilit:
- Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontierJournal of Allergy and Clinical Immunology, 2018
- Inflammation-induced Id2 promotes plasticity in regulatory T cellsNature Communications, 2018
- Immune regulatory cell infusion for graft-versus-host disease prevention and therapyBlood, 2018
- Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous ImmunoglobulinFrontiers in Immunology, 2017
- Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell SubopulationsStem Cell Reviews and Reports, 2016
- GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cellsBlood, 2015
- Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3–positive CD8+ T lymphocytesJournal of Allergy and Clinical Immunology, 2015
- Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties?The International Journal of Cell Cloning, 2014
- Monocytic Myeloid-Derived Suppressor Cells Accumulate in Renal Transplant Patients and Mediate CD4+Foxp3+ Treg ExpansionAmerican Journal of Transplantation, 2013
- Immune Stimulatory Receptor CD40 Is Required for T-Cell Suppression and T Regulatory Cell Activation Mediated by Myeloid-Derived Suppressor Cells in CancerCancer Research, 2010