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

引用

Cellular & Molecular Immunology 2021年第5期18卷 1172-1185页

作者： Huidong Guo Ying-Jun Chang Yan Hong Lan-Ping Xu Yu Wang Xiao-Hui Zhang Ming Wang Huan Chen Yu-Hong Chen Feng-Rong Wang Wei-Han Yu-Qian Sun Chen-Hua Yan Fei-Fei Tang Xiao-Dong Mo Kai-Yan Liu Xiao-Jun Huang Peking University People’s Hospital&Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationNo.11 South Street of XizhimenXicheng District100044BeijingChina Peking-Tsinghua Center for Life Sciences 100871BeijingChina Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences2019RU029BeijingChina

haploidentical stem cell transplantation(haplo-sct)achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation(MSDT)in treating hematological *** define the underlying regulatory dynamics,we analyzed time courses of leukemia burden and immune abundance of haplo-sct or MSDT from multiple ***,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 *** found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia *** 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 ***,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 *** results showed that the haplo-sct slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with *** 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 *** results unraveled the role of immune cells in superior antileukemia effects of haplo-sct compared with MSDT.

关键词： Graft-versus-leukemia haplo-sct MSDT AML MRD

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