Efficiency of human monocyte-derived suppressor cell-based treatment in graft-versus-host disease prevention while preserving graft-versus-leukemia effect

Autor: Andrea Brazdova, Bernard Bonnotte, Philippe Saas, T. Ghesquiere, Maxime Samson, Marine Thébault, Sylvain Audia, Claire Gerard, Claudie Cladière, Hélène Greigert, Nona Janikashvili, Sethi Ouandji, Marion Ciudad, Clovis Boibessot
Rok vydání: 2021
Předmět:
0301 basic medicine
human monocyte-derived suppressor cells
Immunology
Cell
Graft vs Host Disease
immunosuppressive drugs
Inflammation
Mice
SCID
Disease
Monocytes
Mice
03 medical and health sciences
0302 clinical medicine
Mice
Inbred NOD
immune system diseases
graft-versus-host disease
medicine
Animals
Humans
Immunology and Allergy
RC254-282
Original Research
Leukemia
Monocyte derived
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
regulatory t cells
Graft-Versus-Leukemia Effect
RC581-607
medicine.disease
Suppressor cell
surgical procedures
operative
030104 developmental biology
Graft-versus-host disease
medicine.anatomical_structure
Oncology
inflammation
030220 oncology & carcinogenesis
Leukocytes
Mononuclear
graft-versus-leukemia effect
Cancer research
Immunologic diseases. Allergy
medicine.symptom
business
Function (biology)
Research Article
Zdroj: OncoImmunology, Vol 10, Iss 1 (2021)
Oncoimmunology
article-version (VoR) Version of Record
ISSN: 2162-402X
DOI: 10.1080/2162402x.2021.1880046
Popis: Background 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. Methods 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.
Databáze: OpenAIRE
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