髓源抑制性细胞与恶性肿瘤的研究进展

Progress on myeloid derived suppressor cells and cancer

髓源抑制性细胞(myeloid derived suppressor cells,MDSCs)是一群异质性细胞,包括多种处于不同分化阶段的髓样细胞,如髓系祖细胞、未成熟的巨噬细胞、粒细胞、单核细胞、树突状细胞等。在荷瘤小鼠的血液、脾脏和肿瘤组织及肿瘤患者的外周血和肿瘤组织中存在大量MDSCs的扩增,与肿瘤的进展密切相关。恶性肿瘤来源的多种因子如粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)、白细胞介素(interleukin,IL)-6、S100钙结合蛋白A8/A9(S100 calcium binding protein A8/A9,S100A8/A9)等是导致MDSCs扩增的关键因素。MDSCs可通过抑制机体抗肿瘤免疫、上皮-间质转化(epithelial-mesenchymal transition,EMT)、侵袭、血管生成、转移前小生境形成等多种途径导致肿瘤发生发展。本文主要介绍MDSCs的亚群、功能、募集和活化机制,MDSCs作为预后标志物的价值以及当前靶向MDSCs的抗肿瘤治疗策略,以期加深对MDSCs与恶性肿瘤关系的认识。

Myeloid cells are a highly diverse population,including a variety of myeloid cells at different stages of differentiation,such as myeloid progenitor,immature macrophages,granulocytes,monocytes and dendritic cells.There is a large expansion of MDSCs in the blood,spleen and tumor tissues of tumor-bearing mice and the peripheral blood and tumor tissues of cancer patients.MDSCs are closely related to the progress of tumor factors such as GM-CSF,IL-6,S100 A8/A9,which are the key cause leading to the expansion of MDSCs.MDSCs can promote the development and metastasis of tumor by inhibiting anti-tumor immunity,epithelial-mesenchymal transition(EMT),invasion,angiogenesis and drug resistance.In this review,we discuss the MDSCs.classification,biology,mechanisms driving MDSCs accumulation and activation,the value of MDSCs as prognostic marker and the current anti-cancer treatment strategies targeting MDSCs,in order to deepen the understanding of MDSCs in tumor and develop new therapeutic strategies targeting MDSCs.