Ramos, Teresa LopesGarcía-Guerrero, EstefaníaCaballero-Velázquez, TeresaRodríguez-Gil, AlfonsoCaracuel-García, RocíoNufer, MelanieRobles-Frías, María JoséBarbado, María VictoriaPérez-Simón, José A.2022-10-312022-10-312021-09-23Ramos TL, García-Guerrero E, Caballero-Velázquez T, Rodríguez-Gil A, Caracuel-García R, Nufer M, et al. Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease. Bone Marrow Transplant. 2021 Dec;56(12):3049-30580268-3369http://hdl.handle.net/10668/4301In 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Bone marrowLeukemiaProteasome inhibitorIxazomibGraft-versus-host diseaseB cellsMédula óseaLeucemiaInhibidores de proteasomaEnfermedad injerto contra huéspedLinfocitos BMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Tissue Transplantation::Bone Marrow TransplantationMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Boron CompoundsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::GlycineMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host ReactionMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::ImmunityMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Immune System Diseases::Graft vs Host Diseaseresearch article34556806open access10.1038/s41409-021-01452-11476-5365PMC8636253