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髓源性抑制细胞——它们在血液肿瘤恶性肿瘤和其他癌症中的作用,以及对治疗的可能影响。

Myeloid-derived suppressor cells--their role in haemato-oncological malignancies and other cancers and possible implications for therapy.

机构信息

Haematology Unit, Bnai-Zion Medical Centre, Haifa, Israel.

出版信息

Br J Haematol. 2011 Jun;153(5):557-67. doi: 10.1111/j.1365-2141.2011.08678.x. Epub 2011 Apr 8.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells at different stages of maturation that play a role in cancer tolerance and function as an immune-suppressive cell subpopulation. They utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of T cell activation and expansion. Further advances in our understanding of this cell population in both murine models and humans has enabled more accurate characterization of their phenotype and the recognition of two major classes of MDSCs: granulocytic and monocytic. Recently, the mechanism of action and clinical importance of MDSCs has been more clearly defined and their interactions with cancer cells have been shown to be among the factors influencing tumour development and induction of tolerance. Most of the earlier studies were performed using murine models, but recent clinical investigations have shown their potential role in human cancers. Here, we review the origin of MDSCs, their mechanisms of action, the factors influencing their production and related signalling pathways. We focus on their role in human solid tumours and haemato-oncological malignancies, and relate to possible novel therapeutic approaches targeting MDSCs which could be considered together with other anticancer strategies in the not too distant future.

摘要

髓系来源的抑制性细胞(MDSCs)是一种异质性的未成熟髓系细胞群体,处于不同的成熟阶段,在肿瘤耐受中发挥作用,并作为免疫抑制性细胞亚群发挥功能。它们利用不同的机制来阻断先天和适应性抗肿瘤免疫的两个分支,主要通过抑制 T 细胞的激活和扩增。在小鼠模型和人类中对该细胞群体的进一步深入了解,使我们能够更准确地描述其表型,并认识到两种主要类型的 MDSCs:粒细胞和单核细胞。最近,MDSCs 的作用机制及其在临床中的重要性得到了更明确的定义,并且它们与癌细胞的相互作用被证明是影响肿瘤发展和诱导耐受的因素之一。早期的大多数研究都是在小鼠模型中进行的,但最近的临床研究表明它们在人类癌症中具有潜在的作用。在这里,我们综述了 MDSCs 的起源、作用机制、影响其产生的因素及其相关信号通路。我们重点讨论了它们在人类实体瘤和血液恶性肿瘤中的作用,并探讨了针对 MDSCs 的可能的新的治疗方法,这些方法可以与其他抗癌策略一起在不久的将来考虑。

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