在这篇综述文章中，我们概述了针对骨髓增生异常综合征 (MDS) 患者的基于免疫和细胞治疗的方法的当前前景。鉴于通过同种异体造血细胞移植观察到的移植物抗白血病 (GVL) 效应，以及在 MDS 细胞中观察到的已知免疫逃逸机制，人们对开发基于免疫的方法来治疗 MDS 产生了极大的兴趣。这些尝试包括阻断免疫逃逸分子的基于抗体的药物，例如介导 MDS 细胞和 T 淋巴细胞之间相互作用的 PD-1/PD-L1 和 TIM-3/galectin-9 轴抑制剂，以及抗体阻断 CD47/SIRPα 相互作用，介导巨噬细胞吞噬作用。不幸的是，这些方法基本上没有成功。 T 细胞参与疗法和嵌合抗原受体 T (CAR-T) 细胞具有巨大潜力，但这些方法也存在一些 MDS 特有的限制。然而，下一代细胞疗法可能会克服其中许多限制，包括那些采用工程化 T 细胞受体或基于自然杀伤 (NK) 细胞的平台的疗法。无论采用哪种方法，所有这些免疫细胞都受到MDS复杂的骨髓微环境的影响，其中含有促炎细胞因子和免疫抑制成分的可变且异质的混合物。了解这种相互作用对于确保 MDS 免疫和细胞疗法的成功至关重要。版权所有 © 2024 Elsevier Inc. 保留所有权利。

In this review article, we outline the current landscape of immune and cell therapy-based approaches for patients with myelodysplastic syndromes (MDS). Given the well characterized graft-versus-leukemia (GVL) effect observed with allogeneic hematopoietic cell transplantation, and the known immune escape mechanisms observed in MDS cells, significant interest exists in developing immune-based approaches to treat MDS. These attempts have included antibody-based drugs that block immune escape molecules, such as inhibitors of the PD-1/PD-L1 and TIM-3/galectin-9 axes that mediate interactions between MDS cells and T-lymphocytes, as well as antibodies that block the CD47/SIRPα interaction, which mediates macrophage phagocytosis. Unfortunately, these approaches have been largely unsuccessful. There is significant potential for T-cell engaging therapies and chimeric antigen receptor T (CAR-T) cells, but there are also several limitations to these approaches that are unique to MDS. However, many of these limitations may be overcome by the next generation of cellular therapies, including those with engineered T-cell receptors or natural killer (NK)-cell based platforms. Regardless of the approach, all these immune cells are subject to the complex bone marrow microenvironment in MDS, which harbours a variable and heterogeneous mix of pro-inflammatory cytokines and immunosuppressive elements. Understanding this interaction will be paramount to ensuring the success of immune and cellular therapies in MDS.Copyright © 2024 Elsevier Inc. All rights reserved.