Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease
| العنوان: | Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease |
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| المؤلفون: | Teresa L. Ramos, Alfonso Rodríguez-Gil, José Antonio Pérez-Simón, Melanie Nufer, Teresa Caballero-Velázquez, Estefanía García-Guerrero, María Victoria Barbado, Rocío Caracuel-García, María José Robles-Frías |
| المساهمون: | 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, Takeda Pharmaceutical Company, Asociación Española Contra el Cáncer, Centro de Investigación Biomédica en Red Cáncer (España), [Ramos,TL, García-Guerrero,E, Caballero-Velázquez,T, Rodríguez-Gil,A, Caracuel-García,R, Nufer,M, Robles-Frías,MJ, Barbado,MV, Pérez-Simón,JA] Instituto de Biomedicina de Sevilla (IBIS/CSIC), CIBERONC, Universidad de Sevilla, Sevilla, Spain. [Ramos,TL] Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA. [Caballero-Velázquez,T, Pérez-Simón,JA] Department of Hematology, University Hospital Virgen del Rocio, Universidad de Sevilla, Sevilla, Spain., Takeda company (PCRS-2016-101751) partially supported the study, This work has been partially supported by the CIBERONC (CB16/12/00480), and TerCel 16/0011/0035. Spanish Association Against Cancer (AECC-POSTD18023LOPE) fellowship (TLR). |
| المصدر: | Bone Marrow Transplantation Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Graft vs Host Disease, Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host Reaction [Medical Subject Headings], Disease, Graft-versus-host disease, Inhibidores de proteasoma, Ixazomib, Mice, chemistry.chemical_compound, immune system diseases, Organisms::Eukaryota::Animals [Medical Subject Headings], Proteasome inhibitor, Bone Marrow Transplantation, Leukemia, Effector, Médula ósea, Hematology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Tissue Transplantation::Bone Marrow Transplantation [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Glycine [Medical Subject Headings], surgical procedures, operative, medicine.anatomical_structure, Linfocitos B, medicine.drug, Boron Compounds, Bone marrow transplantation, Glycine, Graft vs Leukemia Effect, Enfermedad injerto contra huésped, Article, Immune system, medicine, Animals, Bone marrow, Leucemia, B cells, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Transplantation, business.industry, Immunity, Phenomena and Processes::Immune System Phenomena::Immunity [Medical Subject Headings], Translational research, medicine.disease, Diseases::Immune System Diseases::Graft vs Host Disease [Medical Subject Headings], chemistry, Immunology, business, Chemicals and Drugs::Inorganic Chemicals::Boron Compounds [Medical Subject Headings] |
| الوصف: | 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. Takeda company (PCRS-2016-101751) partially supported the study; This work has been partially supported by the CIBERONC (CB16/12/00480), and TerCel 16/0011/0035. Spanish Association Against Cancer (AECC-POSTD18023LOPE) fellowship (TLR). |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| تدمد: | 1476-5365 0268-3369 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::227fcab3b1ab31aee8f3643f5967ee34Test https://doi.org/10.1038/s41409-021-01452-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....227fcab3b1ab31aee8f3643f5967ee34 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765365 02683369 |
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