ID | 62275 |
FullText URL | |
Author |
Nakamura, Makoto
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
researchmap
Meguri, Yusuke
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ikegawa, Shuntaro
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kondo, Takumi
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sumii, Yuichi
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fukumi, Takuya
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Iwamoto, Miki
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sando, Yasuhisa
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sugiura, Hiroyuki
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Asada, Noboru
Department of Hematology and Oncology, Okayama University Hospital
Kaken ID
researchmap
Ennishi, Daisuke
Department of Hematology and Oncology, Okayama University Hospital
Tomida, Shuta
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Kaken ID
researchmap
Fukuda-Kawaguchi, Emi
REGiMMUNE Corporation
Ishii, Yasuyuki
REGiMMUNE Corporation
Maeda, Yoshinobu
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
researchmap
Matsuoka, Ken-Ichi
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
|
Abstract | Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by alpha -galactosylceramide (alpha -GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of alpha -GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4(+)Foxp3(+) regulatory T cells. These studies indicate that alpha -GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.
|
Published Date | 2021-06-23
|
Publication Title |
Scientific Reports
|
Volume | volume11
|
Issue | issue1
|
Publisher | Nature Research
|
Start Page | 13125
|
ISSN | 2045-2322
|
Content Type |
Journal Article
|
language |
English
|
OAI-PMH Set |
岡山大学
|
Copyright Holders | © The Author(s) 2021
|
File Version | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.1038/s41598-021-92526-z
|
License | http://creativecommons.org/licenses/by/4.0/
|
Funder Name |
Japan Society for the Promotion of Science
|
助成番号 | 20K08753
|