IL-27调控单倍型-脐血移植后免疫重建及移植物抗白血病效应研究

单倍型-脐血移植（haplo-cord SCT）可提高移植预后，减少复发率，但机制未明。课题组前期发现haplo-cord SCT后IL-27水平显著高于单倍型供体移植患者，且IL-27高水平与低复发率、高生存率相关。文献报道IL-27可调节造血干细胞的分化与T细胞的发育和功能，提高抗肿瘤活性。因此我们推测IL-27通过促进移植后免疫重建和细胞毒T细胞功能，增强了移植后的移植物抗白血病（GVL）效应。本课题拟：①通过临床研究，明确移植后IL-27水平与haplo-cord SCT免疫重建及肿瘤负荷间的关系，并探讨移植后IL-27的来源；②利用IL-27敲基因小鼠构建haplo-cord SCT小鼠模型，阐明IL-27影响免疫重建和GVL效应的机制。明确IL-27在haplo-cord SCT中的作用可为其临床应用初步奠定基础，并为揭示haplo-cord SCT的疗效机制提供部分依据。

Haplo-cord SCT may improve the prognosis of haplo-identical donor SCT (haplo SCT), with decreased relapse incidence. However, its therapeutic mechanisms remain indeterminate. Our previous data showed a higher level of IL-27 in patients received haplo-cord SCT compared to those received haplo SCT. Moreover, a higher IL-27 level post-SCT was related to lower relapse incidence and longer survival. It has been reported that IL-27 may regulate the differentiation in hematopoietic stem cells, and the development and function of T cells, which promotes anti-tumor activity. We hypothesize that IL-27 may induce the immune reconstitution post haplo-cord SCT, and thereafter enhance the development and function of cytotoxic T cells, resulting in a more efficient graft-versus-host (GVL) effect. With the support of the grant, firstly we suppose to address the correlation between the IL-27 level and immune reconstitution as well as the level of residual disease by retrospective and prospective clinical studies, and furthermore to reveal the source of IL-27 post haplo-cord SCT. Secondly we plan to establish animal model of haplo-cord SCT involving IL-27p28 gene knockout mouse, in order to investigate the impact and the mechanisms of IL-27 on immune reconstitution and GVL effect post haplo-cord SCT. To determine the role of IL-27 may allow its further exploration of clinical intervention, and meanwhile may partially contribute to clarify the therapeutic mechanism of haplo-cord SCT.