异基因造血干细胞移植后免疫微环境的重建对促进正常造血功能恢复、清除白血病(干)细胞起着至关重要的作用，对移植患者临床转归有关键影响，但目前针对移植后骨髓免疫微环境与干细胞相互作用的系统研究鲜有报道。我们前期研究表明，移植后免疫反应过度，即移植物抗宿主病导致正常造血干细胞/祖细胞(HSC/HPC)向红系巨核系祖细胞(MEP)分化障碍；而免疫反应不足，则白血病(干)细胞发生免疫逃逸导致疾病复发。我们拟在此基础上，进一步从大样本移植患者临床及动物模型两方面入手，研究移植后免疫微环境重建并参与HSC/HPC分化过程中关键细胞、功能基因及信号分子；探索不同免疫微环境应激状态下白血病(干)细胞免疫逃逸相关功能基因及信号通路的分子机制；从而为防治移植后白血病复发、减少移植并发症、促进移植疗效提高提供新的思路；并为免疫微环境与造血干细胞及其恶变而来的白血病干细胞的相互作用模式与机制提供理论基础。

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has advanced to a routine procedure for treating patients with hematological malignancies by redirecting the immune microenvironment. Unfortunately, cure is often hampered by relapse of the underlying disease, graft-versus-host disease, or delayed hematopoietic recovery, which account for the majority of complications after allo-HSCT. Hence, immune microenvironment reconstitution is therefore an area of intensive research. However, the number of studies that exploring the mechanisms for the interaction between “immune niche”, hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are limited. Our preliminary studies demonstrated that excessive immune reactions such as graft-versus-host disease (GvHD) may lead to a block in normal hematopoietic differentiation of HSC proceeds toward common myeloid progenitor (CMP) and megakaryocyte/erythrocyte progenitor (MEP), while, insufficient immune system caused LSCs immune escape, long term dormancy, as well as relapse initiation after HSCT. Based on these findings, in this study, we propose to achieve following objectives by using both patient samples and animal models: to explore the role of immune microenvironment reconstitution after allo-HSCT in HSC/HPC differentiation blockage; to evaluate the biological characteristics and key regulatory mechanisms underlying LSC immune escape. These studies will provide directions on developing interventional strategies to prevent leukemia relapse, and promote hematopoietic recovery after allo-HSCT and in turn to increase curative rate of allo-HSCT.