RT Journal Article
T1 Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease.
A1 Ramos, Teresa Lopes
A1 García-Guerrero, Estefanía
A1 Caballero-Velázquez, Teresa
A1 Rodríguez-Gil, Alfonso
A1 Caracuel-García, Rocío
A1 Nufer, Melanie
A1 Robles-Frías, María José
A1 Barbado, María Victoria
A1 Pérez-Simón, José A
AB 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.
YR 2021
FD 2021-09-23
LK https://hdl.handle.net/10668/27863
UL https://hdl.handle.net/10668/27863
LA en
DS RISalud
RD Apr 8, 2025