CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The impact of regulatory T cells on the graft-versus-leukemia effect.
The impact of regulatory T cells on the graft-versus-leukemia effect.
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异基因造血干细胞移植(allo-HSCT)是许多血液系统恶性肿瘤的唯一治愈性疗法,其中移植物抗白血病(GVL)效应在控制复发中发挥关键作用。
然而,GVL 的成功受到移植物抗宿主病(GVHD)的阻碍,即供者 T 细胞攻击受者的健康组织。天然调节性 T 细胞(Treg)抑制免疫应答的能力已被用作对抗 GVHD 的治疗选择。
然而,评估 Treg 抑制 GVHD 的能力是否不会损害 GVL 的获益至关重要。动物模型的初步研究表明,Treg 可以减轻 GVHD 同时保留 GVL,但结果因肿瘤类型而异。使用 Treg 作为 GVHD 预防或治疗的人体试验显示出令人鼓舞的结果,强调了输注时机和 Treg/Tcon 比例的重要性。在这篇综述中,我们讨论了可用于增强 Treg 输注后 GVL 的策略,以及过继性 Treg 转移后维持 GVL 效应的拟议机制。为了优化 allo-HSCT 中 Treg 给药的治疗结局,未来的努力应集中于改进用于输注的 Treg 来源,并评估其对介导 GVHD 的抗原的特异性,同时保留 GVL 应答。
Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only curative therapy for many hematologic malignancies, whereby the Graft-versus-Leukemia (GVL) effect plays a pivotal role in controlling relapse.
However, the success of GVL is hindered by Graft-versus-Host Disease (GVHD), where donor T cells attack healthy tissues in the recipient. The ability of natural regulatory T cells (Treg) to suppress immune responses has been exploited as a therapeutical option against GVHD. Still, it is crucial to evaluate if the ability of Treg to suppress GVHD does not compromise the benefits of GVL. Initial studies in animal models suggest that Treg can attenuate GVHD while preserving GVL, but results vary according to tumor type.
Human trials using Treg as GVHD prophylaxis or treatment show promising results, emphasizing the importance of infusion timing and Treg/Tcon ratios. In this review, we discuss strategies that can be used aiming to enhance GVL post-Treg infusion and the proposed mechanisms for the maintenance of the GVL effect upon the adoptive Treg transfer.
In order to optimize the therapeutic outcomes of Treg administration in allo-HSCT, future efforts should focus on refining Treg sources for infusion and evaluating their specificity for antigens mediating GVHD while preserving GVL responses.
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