Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease

descriptionPublicationkeyboard_double_arrow_right Article 23 Sep 2021 Spain English Publisher:Springer Science and Business Media LLCJournal:Bone Marrow Transplantation, volume 56, pages 3,049-3,058 (issn: 0268-3369, eissn: 1476-5365,

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Authors: Teresa Lopes Ramos; Estefanía García-Guerrero; Teresa Caballero-Velázquez; Alfonso Rodríguez-Gil; Rocío Caracuel-García; Melanie Nufer; María José Robles-Frías; +2 Authors

doi: 10.1038/s41409-021-01452-1

pmid: 34556806

pmc: PMC8636253

handle: 11441/137780 , 10668/4301 , 10261/269461

Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease

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Abstract

AbstractIn this study, we aimed to modify the immune response in the long term after allogeneic bone marrow transplantation (allo-BMT) by using the proteasome inhibitor ixazomib (IXZ) at the late stages of the post-transplant period. This approach facilitated the immune reconstitution after transplantation. IXZ significantly prolonged survival and decreased the risk of chronic graft-versus-host disease (cGvHD) in two different murine models without hampering the graft-versus-leukemia (GvL) effect, as confirmed by bioluminescence assays. Remarkably, the use of IXZ was related to an increase of regulatory T cells both in peripheral blood and in the GvHD target organs and a decrease of effector donor T cells. Regarding B cells, IXZ treated mice had faster recovery of B cells in PB and of pre-pro-B cells in the bone marrow. Mice receiving ixazomib had a lower number of neutrophils in the GvHD target organs as compared to the vehicle group. In summary, delayed administration of IXZ ameliorated cGvHD while preserving GvL and promoted a pro-tolerogenic immune response after allo-BMT.

Country

Spain

Related Organizations

University of Seville
Spain
Universidad de Sevilla (US)
Spain
Stanford University
United States
Hospital Universitario Virgen del Rocío
Spain
Institute of Biomedicine of Seville
Spain

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Keywords

Medical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immunity, Boron Compounds, Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Boron Compounds, Glycine, Graft vs Host Disease, Graft vs Leukemia Effect, Enfermedad injerto contra huésped, Article, Inhibidores de proteasoma, Mice, Animals, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Glycine, Leucemia, Bone Marrow Transplantation, Medical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host Reaction, Médula ósea, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Tissue Transplantation::Bone Marrow Transplantation, Immunity, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice, Medical Subject Headings::Organisms::Eukaryota::Animals, Medical Subject Headings::Diseases::Immune System Diseases::Graft vs Host Disease, Linfocitos B

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