树突状细胞在干扰素联合供体淋巴细胞输注治疗移植后白血病复发中增强抗白血病效应的机制研究

异基因造血干细胞移植术后复发的急性白血病（AL）患者缺乏有效治疗手段，预后恶劣，是临床急需解决的一大难题。近来本课题组在国际上创新性的应用干扰素-α（IFN-α）联合供体淋巴细胞输注（aDLI）治疗移植后复发的对化疗或常规DLI无效的高危AL，81.3%的患者获得完全缓解，3年无白血病生存率达48.6%，疗效远优于常规DLI。但确切机制尚待研究。预试验结果显示IFN-α可能通过有效活化树突状细胞（DC），达到增强抗原提呈，增强效应细胞的活化和杀伤效应。本课题拟用病患标本，离体细胞培养和小鼠模型，从IFN-α诱导的DC(IFN-DC)的表型特征，功能（抗原提呈，促Th1极化，促抗原特异性CD8+ CTL活化增殖，细胞毒性，移行能力）及其成熟活化的相关分子机制，研究IFN-DC在aDLI治疗中增强抗白血病效应的可能机制，为设计更优化、更有效的新型过继免疫治疗方案提供理论依据。

Acute leukemia (AL) relapse is the leading cause of death following allogeneic stem cell transplantation (allo-HSCT) and the overall survival is poor due to lack of effective treatment. Our group pioneered a novel strategy using donor lymphocyte infusion (DLI) in combination with interferon-α (IFN-α).We demonstrated that the combination of IFN-α with DLI (aDLI) significantly improved the therapeutic efficacy compared to traditional DLI (tDLI). Our data showed that in the group of aDLI,the complete remission (CR) rate and 3-year leukemia free survival (LFS) was 81.3% and 48.6% respectively.Furthermore, our preliminary results showed that IFN-α could enhance the anti-leukemia effects of donor lymphocyte via the activation of dendritic cell (DC) and subsequent enhancement of antigen- presentation and cytotoxity of T cells. However, the detailed mechanisms remain unknown. In this study, we will investigate the association between the activation and maturation of IFN-α-induced DC (IFN-DC) and the enhanced anti-leukemia effects in aDLI treatment using both in vitro and in vivo models as well as clinical specimen. Moreover, we will also elucidate the molecular mechanisms underlying the induction of IFN-DC activation and maturation triggered by IFN-α.We believe that the results of this research will provide valuable theoretical information for designing more optimal and effective adoptive immunotherapy in the future.