Inhibition of the differentiation of dendritic cells from CD34+ progenitors by tumor cells:: Role of interleukin-6 and macrophage colony-stimulating factor
Inhibition of the differentiation of dendritic cells from CD34+ progenitors by tumor cells:: Role of interleukin-6 and macrophage colony-stimulating factor
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DOI：
10.1182/blood.v92.12.4778
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发表时间：
1998-12-15
期刊：
影响因子：
20.3
通讯作者：
Blay, JY
中科院分区：
文献类型：
--
作者：
Menetrier-Caux, C;Montmain, G;Blay, JY
恶性细胞逃避针对肿瘤的免疫应答可能是由于专职抗原呈递细胞（APC）即树突状细胞（DC）的分化或功能缺陷所致。为了验证这一假设，在体外研究了人肾细胞癌细胞系（RCC）对CD 34（+）祖细胞发育为DC的影响。发现RCC细胞系释放可溶性因子，其抑制CD 34（+）细胞分化为DC并触发其向具有有效吞噬能力但缺乏APC功能的单核细胞（CD 14（+）CD 64（+）CD 1a（-）CD 86（-）CD 80（-）HLA-DR低）的定向分化。发现RCC CM通过抑制[CD 14（+）CD 1a（-）]前体分化为DC和阻断[CD 14（-）CD 1a（+）]衍生DC获得APC功能，作用于培养第6天出现的两个不同亚群（[CD 14（+）CD 1a（-）]和[CD 14（-）CD 1a（+）]）。白细胞介素-6（IL-6）和巨噬细胞集落刺激因子（M-CSF）的作用与此有关：抗IL-6和M-CSF的抗体可消除RCC CM的抑制作用，重组IL-6和/或M-CSF可抑制DC的分化，其作用与RCC CM相似。RCC CM对DC分化的抑制作用是通过诱导M-CSF受体介导的CD 34（+）细胞表面的粒细胞-巨噬细胞集落刺激因子受体α（M-CSFR; CD 115）和粒细胞-巨噬细胞集落刺激因子受体α（GM-CSFR α; CD 116）表达的丧失，这两种现象分别被抗IL-6/IL-6 R和抗M-CSF抗体逆转。最后，一组产生IL-6和M-CSF的肿瘤细胞系诱导了类似的效果。总之，结果表明，DC发育的抑制可能代表肿瘤细胞逃避免疫识别的常见机制。(C)1998年，美国血液学会。
The escape of malignant cells from the immune response against the tumor may result from a defective differentiation or function of professional antigen-presenting cells (APC), ie, dendritic cells (DC). To test this hypothesis, the effect of human renal cell carcinoma cell lines (RCC) on the development of DC from CD34(+) progenitors was investigated in vitro. RCC cell lines were found to release soluble factors that inhibit the differentiation of CD34(+) cells into DC and trigger their commitment towards monocytic cells (CD14(+)CD64(+)CD1a(-)CD86(-)CD80(-)HLA-DRlow) with a potent phagocytic capacity but lacking APC function. RCC CM were found to act on the two distinct subpopulations emerging in the culture at day 6 ([CD14(+)CD1a(-)] and [CD14(-)CD1a(+)]) by inhibiting the differentiation into DC of [CD14(+)CD1a(-)] precursors and blocking the acquisition of APC function of the [CD14(-)CD1a(+)] derived DC. Interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) were found to be responsible for this phenomenon: antibodies against IL-6 and M-CSF abrogated the inhibitory effects of RCC CM; and recombinant IL-6 and/or M-CSF inhibited the differentiation of DC similarly to RCC CM, The inhibition of DC differentiation by RCC CM was preceeded by an induction of M-CSF receptor (M-CSFR; CD115) and a loss of granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFR alpha; CD116) expression at the surface of CD34(+) cells, two phenomenon reversed by anti-IL-6/IL-6R and anti-M-CSF antibodies, respectively. Finally, a panel of tumor cell lines producing IL-6 and M-CSF induced similar effects. Taken together, the results suggest that the inhibition of DC development could represent a frequent mechanism by which tumor cells will escape immune recognition. (C) 1998 by The American Society of Hematology.