Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation

Autor: Xiao-Hui Zhang, Yu-Qian Sun, Yu-Hong Chen, Feng-Rong Wang, Huan Chen, Yan Hong, Ying-Jun Chang, Kai-Yan Liu, Huidong Guo, Fei-Fei Tang, Wei-Han, Xiao-Jun Huang, Chen-Hua Yan, Ming Wang, Xiao-Dong Mo, Yu Wang, Lan-Ping Xu
Rok vydání: 2021
Předmět:
Adult
0301 basic medicine
endocrine system
Adolescent
Immunology
Graft vs Host Disease
Apoptosis
Human leukocyte antigen
Young Adult
03 medical and health sciences
0302 clinical medicine
Immune system
hemic and lymphatic diseases
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
Medicine
Child
business.industry
Histocompatibility Testing
Siblings
Comment
Hematopoietic Stem Cell Transplantation
Myeloid leukemia
Middle Aged
Allografts
medicine.disease
Minimal residual disease
Tissue Donors
Killer Cells
Natural
Mice
Inbred C57BL
Transplantation
Kinetics
Leukemia
Myeloid
Acute
Leukemia
surgical procedures
operative
030104 developmental biology
Infectious Diseases
Child
Preschool
Multivariate Analysis
Transplantation
Haploidentical
Disease Progression
Cancer research
Cytokines
Cytokine secretion
business
T-Lymphocytes
Cytotoxic
030215 immunology
Zdroj: Cell Mol Immunol
ISSN: 2042-0226
1672-7681
DOI: 10.1038/s41423-020-00597-1
Popis: Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.
Databáze: OpenAIRE
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