Artículo
Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease
Autor/es | Ramos, Teresa L.
García Guerrero, Estefanía Caballero Velázquez, Teresa Rodríguez Gil, Alfonso Caracuel García, Rocío Nufer, Melanie Robles Frías, María José Barbado González, Mª Victoria Pérez Simón, José Antonio |
Departamento | Universidad de Sevilla. Departamento de Medicina Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica |
Fecha de publicación | 2021-09-23 |
Fecha de depósito | 2022-10-10 |
Publicado en |
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Resumen | In 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 ... In 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. |
Cita | Ramos, T.L., García Guerrero, E., Caballero Velázquez, T., Rodríguez Gil, A., Caracuel García, R., Nufer, M.,...,Pérez Simón, J.A. (2021). Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease. Bone Marrow Transplantation, 56 (12), 3049-3058. https://doi.org/10.1038/s41409-021-01452-1. |
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