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异基因造血干细胞移植背景下的髓源性抑制细胞。

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation.

机构信息

Hematology Department, CHRU Nancy, Université de Lorraine, Nancy, France.

Université de Lorraine, UMR 7365 CNRS, IMoPA, Nancy, France.

出版信息

Front Immunol. 2020 May 22;11:989. doi: 10.3389/fimmu.2020.00989. eCollection 2020.

Abstract

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the recipient, after allo-HSCT) might mediate immune suppression through multiple mechanisms. However, it remains unclear how MDSCs can be distinguished from their normal myeloid counterparts in the hematopoietic stem cell donor graft and during immune reconstitution after allo-HSCT in the recipient. Our ability to understand their exact role in allo-HSCT is limited by the absence of a specific gene signature or surface markers for identifying MDSCs among myeloid cells and by their plasticity in different microenvironments. According to various studies, MDSCs might induce transplant tolerance and control graft vs. host disease (GVHD), but their impact on the graft vs. tumor effect (GVT) is not fully understood. In fact, we know that MDSCs commonly expand in patients with cancer, and they are thought to promote hematological malignancy progression. However, little is known about whether depleting them might be an effective strategy for enhancing GVT effects. Here, we review data published over the past 40 years on allo-HSCT to delineate the different MDSC subsets, and their abilities to induce transplant tolerance and preserve the GVT effect. This review will provide a basis for determining whether one MDSC subset might be proposed as the most appropriate candidate for cellular therapies, due to its ability to modulate GVHD.

摘要

髓系来源的抑制性细胞(MDSCs)是一种先天免疫细胞,具有抑制适应性免疫反应的能力。在异基因造血干细胞移植(allo-HSCT)的背景下,MDSCs(在供体移植物中,以及在 allo-HSCT 后受体中)可能通过多种机制介导免疫抑制。然而,目前尚不清楚如何在造血干细胞供体移植物中以及受体 allo-HSCT 后的免疫重建过程中,将 MDSCs 与其正常髓系细胞区分开来。由于缺乏用于在髓系细胞中识别 MDSCs 的特定基因特征或表面标志物,以及它们在不同微环境中的可塑性,我们对其确切作用的理解能力受到限制。根据各种研究,MDSCs 可能诱导移植耐受并控制移植物抗宿主病(GVHD),但其对移植物抗肿瘤效应(GVT)的影响尚未完全了解。事实上,我们知道 MDSCs 通常在癌症患者中扩增,并且被认为促进血液恶性肿瘤的进展。然而,对于清除它们是否可能是增强 GVT 效应的有效策略,我们知之甚少。在这里,我们回顾了过去 40 年来发表的关于 allo-HSCT 的数据,以描绘不同的 MDSC 亚群及其诱导移植耐受和保留 GVT 效应的能力。这篇综述将为确定一个 MDSC 亚群是否可以作为细胞治疗的最佳候选者提供依据,因为其具有调节 GVHD 的能力。

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