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首页> 外文期刊>Journal of immunotherapy >Differential immunologic and microRNA effects of 2 dosing regimens of recombinant human granulocyte/macrophage colony stimulating factor
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Differential immunologic and microRNA effects of 2 dosing regimens of recombinant human granulocyte/macrophage colony stimulating factor

机译：两种重组人粒细胞/巨噬细胞集落刺激因子给药方案的差异免疫学和microRNA效应

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Recombinant human (rh) granulocyte/macrophage colony stimulating factor (GM-CSF) has demonstrated antitumor immunologic activity in prostate and other cancers. Dosing has been empiric, and biomarkers of effect have not been established. Eight patients with biochemical relapse of prostate cancer were randomized into group A, in which they received rhGM-CSF at 250 μg/m days 1-14 of a 28-day cycle, and 8 were randomized into group B, in which they received 250 μg 3 times a week continuously. Blood dendritic cell (DC), immune suppressor cell, cytokine, and microRNA (miR) levels were examined using flow cytometric, enzyme-linked immunosorbent, and/or polymerase chain reaction-based assays. Group A had greater increases in myeloid DC and in granulocyte and monocytes. In croup B, plasmacytoid DC decreased. In group A, DC production of interleukin-12 relative to interleukin-10 decreased; this ratio increased in group B. Increases in myeloid-derived suppressor cells were observed in both the groups with increases greater in group A. Increases in regulatory T cells and in serum tumor necrosis and vascular endothelial growth factors were only observed in group A. Serum miR-155 decreased in group A. An increase in serum miR-223 and a decrease in miR-125b and miR-146a were observed in group B. The dosing of rhGM-CSF influences immune and miR effects. More DC activation and fewer myeloid-derived suppressor and regulatory T cells are observed when administered at lower doses intermittently and continuously compared with when administered at higher doses daily and cyclically. Serum levels of miRs are potentially useful biomarkers of these effects.
机译：重组人（rh）粒细胞/巨噬细胞集落刺激因子（GM-CSF）已证明在前列腺癌和其他癌症中具有抗肿瘤免疫活性。剂量是经验性的，尚未建立有效的生物标志物。将8例前列腺癌生化复发患者随机分为A组，在28天周期的1-14天中以250μg/ m 2天接受rhGM-CSF的治疗，将8例随机分为B组，其中接受250例rGM-CSF。微克每周连续3次。使用流式细胞仪，酶联免疫吸附剂和/或基于聚合酶链反应的检测方法检查血液树突状细胞（DC），免疫抑制细胞，细胞因子和microRNA（miR）的水平。 A组的髓样DC以及粒细胞和单核细胞的增加更大。在人群B中，浆细胞样DC降低。在A组中，白介素12相对于白介素10的DC产生减少;该比例在B组中增加。在两个组中均观察到了髓样抑制细胞的增加，而在A组中则有所增加。仅在A组中观察到调节性T细胞以及血清肿瘤坏死和血管内皮生长因子的增加。 A组中miR-155降低。B组中观察到血清miR-223升高以及miR-125b和miR-146a降低。rhGM-CSF的剂量影响免疫和miR效应。与每天和周期性地以较大剂量给药相比，间歇性和连续以较低剂量给药时，观察到更多的DC活化和较少的髓样来源的抑制性T细胞和调节性T细胞。血清中miR的水平可能是这些作用的有用生物标志物。

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