TY - JOUR
T1 - Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease
AU - Ramos, Teresa Lopes
AU - García-Guerrero, Estefanía
AU - Caballero-Velázquez, Teresa
AU - Rodríguez-Gil, Alfonso
AU - Caracuel-García, Rocío
AU - Nufer, Melanie
AU - Robles-Frías, María José
AU - Barbado, María Victoria
AU - Pérez-Simón, José A.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
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.
UR - https://www.scopus.com/pages/publications/85115362207
U2 - 10.1038/s41409-021-01452-1
DO - 10.1038/s41409-021-01452-1
M3 - Article
C2 - 34556806
AN - SCOPUS:85115362207
SN - 0268-3369
VL - 56
SP - 3049
EP - 3058
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 12
ER -