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

Teresa Lopes Ramos, Estefanía García-Guerrero, Teresa Caballero-Velázquez, Alfonso Rodríguez-Gil, Rocío Caracuel-García, Melanie Nufer, María José Robles-Frías, María Victoria Barbado, José A. Pérez-Simón*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3049-3058
Number of pages10
JournalBone Marrow Transplantation
Volume56
Issue number12
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

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