研究概要
供者淋巴细胞输注(DLI)是异基因造血细胞移植后复发髓系恶性肿瘤的关键治疗策略,利用移植物抗白血病(GvL)效应恢复免疫控制。
中文摘要
供者淋巴细胞输注(DLI)是异基因造血细胞移植后髓系恶性肿瘤复发的重要治疗策略,利用移植物抗白血病(GvL)效应恢复免疫控制。尽管在慢性髓性白血病中高度有效,但其在急性髓性白血病中的疗效仍然有限,潜在机制尚未完全明了。Maurer及其同事最近的研究利用前沿技术剖析了骨髓微环境中的免疫-白血病相互作用,鉴定出一群细胞毒性CD8+ T细胞是抗白血病反应的关键介质。该研究强调,在应答者中T细胞和NK细胞动态扩增,而无应答者则表现出免疫抑制性骨髓微环境。T细胞受体追踪显示,急性髓性白血病中GvL的主要效应细胞来源于DLI,但其激活依赖于允许性的骨髓微环境。这些见解强调,白血病进展和免疫反应不仅由恶性细胞塑造,还受到更广泛的微环境动态的影响。需要进一步研究来明确驱动细胞治疗应答或耐药的不同机制,同时也要剖析介导GvL的T细胞的抗原特异性,并确定预测DLI应答的生物标志物。
展开英文摘要原文
Donor lymphocyte infusion (DLI) is a crucial therapeutic strategy for relapsed myeloid malignancies after allogeneic hematopoietic cell transplantation, leveraging the graft-versus-leukemia (GvL) effect to restore immune control. Although highly effective in chronic myeloid leukemia, its efficacy in acute myeloid leukemia remains limited, with underlying mechanisms not fully understood. Recent research by Maurer and colleagues utilized cutting-edge technologies to dissect immune-leukemia interactions within the bone marrow niche, identifying a cytotoxic CD8+ T-cell population as a key mediator of the antileukemic response. The study highlights a dynamic expansion of T and NK cells in responders, whereas nonresponders display an immune suppressive bone marrow niche. T-cell receptor tracking revealed that the primary effectors of GvL in acute myeloid leukemia originate from the DLI, yet their activation depends on a permissive bone marrow microenvironment. These insights emphasize that leukemia progression and immune response are shaped not only by malignant cells but also by broader niche dynamics. Further investigation is needed to define the different mechanisms that drive response or resistance to cellular therapies but also to dissect the antigenic specificity of GvL-mediating T cells and define biomarkers predicting response to DLI.
论文信息
- 作者
- Orofino G、Toffalori C、Vago L
- 单位
- Unit of Immunogenetics, Leukemia Genomics and Immunobiology, IRCCS San Raffaele Scientific Institute, Milano, Italy.Italy
- 期刊
- Cancer research2025 May 2