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在多发性骨髓瘤患者中,髓源性抑制细胞在数量、功能和表型上存在差异。

Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma.

作者信息

Favaloro James, Liyadipitiya Tulita, Brown Ross, Yang Shihong, Suen Hayley, Woodland Narelle, Nassif Najah, Hart Derek, Fromm Phillip, Weatherburn Claire, Gibson John, Ho P Joy, Joshua Douglas

机构信息

Institute of Haematology, Royal Prince Alfred Hospital , Sydney, NSW , Australia.

出版信息

Leuk Lymphoma. 2014 Dec;55(12):2893-900. doi: 10.3109/10428194.2014.904511. Epub 2014 May 12.

Abstract

Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells that have been implicated as inhibitors of lymphopoiesis in patients with malignancies. They have a consensus phenotype of CD33+/CD11b+/HLA-DRlo/- and can be further divided into CD15 + granulocytic (G-MDSC) and CD14 + monocytic (M-MDSC) subsets. We characterized MDSCs in patients with multiple myeloma (MM) and found a significant increase in G-MDSCs in the blood of patients with progressive MM. Flow-sorted MDSCs from patients with MM induced the generation of regulatory T cells (Treg). MDSCs from both patients with MM and aged-matched controls demonstrated a dose-dependent inhibition of lymphocyte proliferation in carboxyfluorescein succinimidyl ester (CFSE)-tracking experiments. Granulocyte colony stimulating factor (G-CSF) administered to induce stem cell mobilization caused an increase in the number of MDSCs in the peripheral blood of patients with MM and a concentration of these immune-suppressive cells in peripheral blood stem cell collections. MDSCs are likely to cause immune dysfunction in patients with MM.

摘要

髓源性抑制细胞(MDSCs)是一类异质性细胞群,在恶性肿瘤患者中被认为是淋巴细胞生成的抑制剂。它们具有CD33+/CD11b+/HLA-DRlo/-的共同表型,可进一步分为CD15 + 粒细胞性(G-MDSC)和CD14 + 单核细胞性(M-MDSC)亚群。我们对多发性骨髓瘤(MM)患者的MDSCs进行了特征分析,发现进展期MM患者血液中的G-MDSCs显著增加。来自MM患者的流式分选MDSCs诱导了调节性T细胞(Treg)的产生。在羧基荧光素琥珀酰亚胺酯(CFSE)追踪实验中,MM患者和年龄匹配对照的MDSCs均表现出对淋巴细胞增殖的剂量依赖性抑制。用于诱导干细胞动员的粒细胞集落刺激因子(G-CSF)导致MM患者外周血中MDSCs数量增加,并且这些免疫抑制细胞在外周血干细胞采集中富集。MDSCs可能导致MM患者出现免疫功能障碍。

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