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髓系恶性肿瘤中的间充质干细胞:聚焦免疫逃逸及治疗意义

Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications.

作者信息

Fracchiolla Nicola Stefano, Fattizzo Bruno, Cortelezzi Agostino

机构信息

UO Onco-Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20100 Milano, Italy.

出版信息

Stem Cells Int. 2017;2017:6720594. doi: 10.1155/2017/6720594. Epub 2017 Aug 21.

Abstract

The importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia. Furthermore, the immune system, both adaptive and innate, encompassing mesenchymal-derived cells, has been shown to take part to the leukemic niche. Here, we critically review the state of art about mesenchymal stem cell role in myelodysplastic syndromes and acute myeloid leukemia, focusing on immune escaping mechanisms as a target for available and future anticancer therapies.

摘要

骨髓微环境在生理性造血过程中形成所谓的龛位,其重要性已广为人知,并且最近的证据支持在血液系统恶性肿瘤中存在从分子水平到细胞结构水平的基质改变。肿瘤来源的间充质干细胞在细胞黏附、代谢、细胞因子信号传导、自噬和甲基化模式方面存在各种改变,这些改变促成了白血病许可龛位的形成。这种龛位既允许骨髓增生异常综合征典型的无效造血,也允许分化停滞、增殖优势以及克隆选择,而克隆选择是急性髓系白血病的标志。此外,包括间充质来源细胞的适应性和先天性免疫系统已被证明参与白血病龛位的形成。在此,我们批判性地综述了间充质干细胞在骨髓增生异常综合征和急性髓系白血病中作用的现有研究状况,重点关注免疫逃逸机制,将其作为现有及未来抗癌治疗的靶点。

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