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

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 

机构地区：[1]Peking University People’s Hospital&Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,No.11 South Street of Xizhimen,Xicheng District,100044,Beijing,China [2]Peking-Tsinghua Center for Life Sciences,100871,Beijing,China [3]Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies,Chinese Academy of Medical Sciences,2019RU029,Beijing,China

出　　处：《Cellular & Molecular Immunology》2021年第5期1172-1185,共14页中国免疫学杂志（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(2017YFA0104500);the Beijing Municipal Science and Technology Commission(Z181100009618032);the National Natural Science Foundation of China(Grant No.81621001,81530046,81770189,81670186,81870141 and 82070185);CAMS Innovation Fund for Medical Sciences(CIFMS)(grant number:2019-I2M-5-034);the Peking University Clinical Scientist Program(BMU2019LCKXJ003).

摘　　要：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.

关 键 词：GRAFT-VERSUS-LEUKEMIA Haplo-SCT MSDT AML MRD 

分 类 号：R733.7[医药卫生—肿瘤]