Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patients
Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patients
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DOI：
10.1002/ijc.11379
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发表时间：
2003-11-01
影响因子：
6.4
通讯作者：
Roth, MD
中科院分区：
文献类型：
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作者：
Kiertscher, SM;Gitlitz, BJ;Roth, MD
在人类外周血中可以鉴定出两种罕见的具有树突状细胞前体(PreDC)特征的细胞。前DC 1是人类白细胞抗原DR‘/CD11 1c(+)细胞，可成熟为DC 1，能够刺激Th1反应。相反，前DC 2是成熟后促进Th2应答的HLA-DR+/CD11 1c(-)/CD123(+)细胞。我们假设DC 1的生长因子GM-CSF和IL-4在体内可以特异性地增加循环DC I的数量和功能。晚期转移性肿瘤患者给予GM-CSF(2.5 mg/kg/d)和IL-4(4或6 mg/kg/d)治疗7天。最高剂量的细胞因子可使前DC 2细胞数平均增加2.3倍，而前DC 1细胞数增加6.5倍，使循环前DC 1/前DC 2比值由治疗前的1.4：1增加到治疗后的4.3：1。体内治疗后DC-1前体细胞较治疗前更大、更复杂，表达更高水平的HLA-DR、CD11c和CD80。从接受GM-CSF/IL-4治疗的患者外周血中分离出的DC 1显示出与患者使用GM-CSF和IL-4治疗前的血液在体外产生的单核细胞来源的DC相当的MLR活性。结论：全身应用GM-CSF和IL-4可在体内优先扩增和成熟DC-1前体群。这些效应与抗原递呈活性有关，为全身GM-CSF和IL-4在体内刺激抗肿瘤免疫提供了一种机制。(C)2003年Wiley-Liss，Inc.
Two rare populations of cells with the features of dendritic cell precursors (preDC) can be identified in human peripheral blood. PreDC 1 are HLA-DR'/CD 1 1c(+) cells which mature into DC 1 capable of stimulating Th1 responses. In contrast, preDC 2 are HLA-DR+/CD 1 1c(-)/CD123(+) cells that promote Th2 responses when matured into DC 2. We hypothesized that administration of GM-CSF and IL-4, growth factors for DC 1, would specifically augment the number and function of circulating DC I in vivo. Patients with advanced metastatic cancer were treated with GM-CSF (2.5 mug/kg/day) and IL-4 (4 or 6 mug/kg/day) for 7 days. Cytokine administration at the highest IL-4 dose produced an average 2.3-fold increase in preDC 2 number, but a 6.5-fold increase in preDC 1, resulting in an increased ratio of circulating preDC 1:preDC 2 from 1.4:1 pre-treatment to 4.3:1 after cytokine therapy. DC 1 precursors identified after in vivo therapy were larger, more complex and expressed higher levels of HLA-DR, CD 1 1c and CD 80 than pre-treatment cells. DC 1 isolated from the peripheral blood of patients receiving GM-CSF/IL-4 therapy demonstrated MLR activity comparable to that of monocyte-derived DC generated in vitro from the patients' pre-treatment blood using GM-CSF and IL-4. We conclude that systemic administration of GM-CSF and IL-4 preferentially expands and matures the preDC 1 population in vivo. These effects correlate with antigen-presenting activity, providing a mechanism by which systemic GM-CSF and IL-4 might stimulate anti-tumor immunity in vivo. (C) 2003 Wiley-Liss, Inc.