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可手术乳腺癌患者功能失调、无反应性单核细胞来源树突状细胞的体外恢复与激活：干扰素-α的关键作用

Ex vivo recovery and activation of dysfunctional, anergic, monocyte-derived dendritic cells from patients with operable breast cancer: critical role of IFN-alpha.

作者信息

Satthaporn Sukchai, Aloysius Mark M, Robins Richard A, Verma Chandan, Chuthapisith Suebwong, McKechnie Alasdair J, El-Sheemy Mohamad, Vassanasiri Wichai, Valerio David, Clark David, Jibril Jibril A, Eremin Oleg

机构信息

Section of Surgery, Queen's Medical Centre, Nottingham University Hospitals, Nottingham, UK.

出版信息

BMC Immunol. 2008 Jun 27;9:32. doi: 10.1186/1471-2172-9-32.

DOI:10.1186/1471-2172-9-32
PMID:18588665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2447825/
Abstract

BACKGROUND

Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses.

RESULTS

Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-alpha+IFN-alpha) or 3 CCM (GM-CSF+IL-4+TNF-alpha) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001).

CONCLUSION

Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-alpha. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-alpha. However, 4 CCM containing IFN-alpha generated-PBDCs, do not produce and secrete IL-12p70 in vitro.

摘要

背景

树突状细胞（DCs）在启动有效的细胞介导免疫反应中起关键作用，但在乳腺癌中功能失调且呈无反应状态。逆转这种功能失调并建立最佳的DC功能是诱导有效的抗癌免疫反应的关键前提。

结果

分别使用4种细胞因子条件培养基（CCM）（GM-CSF+IL-4+TNF-α+IFN-α）或3种CCM（GM-CSF+IL-4+TNF-α）从外周血单核细胞（PBMs）和淋巴结单核细胞（LNMs）的贴壁培养物中体外生成的外周血DCs（PBDCs）和淋巴结DCs（LNDCs），在混合淋巴细胞DC反应（MLDCR，p<0.001）中显示出显著更高的恢复程度和功能能力，与使用2种CCM（GM-CSF+IL-4）或单独培养基从PBMs和LNMs生成的DCs相比，表达显著更高水平的HLA-DR、CD86（p<0.001）。与使用2种CCM或单独培养基从单核细胞生成的PBDCs相比，用3种CCM或4种CCM生成的PBDCs显示出显著（p<0.001）增强的巨吞饮能力（葡聚糖颗粒），并在体外诱导白细胞介素-12p40（IL-12p40）的产生和分泌增加（p<0.001）。与未用脂多糖（LPS）刺激的对照DCs相比，用4种CCM生成的PBDCs经LPS刺激后显示出IL-6分泌增强，但IL-12p70未增强（p<0.001）。

结论

通过使用含有IFN-α的4种CCM对前体贴壁单核细胞进行体外培养，可最佳地逆转可手术乳腺癌患者功能失调且呈无反应状态的PBDCs和LNDCs。在存在IFN-α的情况下，可观察到DCs的最大免疫表型恢复和功能重新激活。然而，含有IFN-α生成的PBDCs在体外不产生和分泌IL-12p70。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/8f661d3efafc/1471-2172-9-32-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/8f09b3ddb23d/1471-2172-9-32-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/4ea618a1b012/1471-2172-9-32-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/daf24c1ca587/1471-2172-9-32-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/3d568cc06f5a/1471-2172-9-32-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/52c7d215c618/1471-2172-9-32-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/8f661d3efafc/1471-2172-9-32-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/8f09b3ddb23d/1471-2172-9-32-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/4ea618a1b012/1471-2172-9-32-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/daf24c1ca587/1471-2172-9-32-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/3d568cc06f5a/1471-2172-9-32-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/52c7d215c618/1471-2172-9-32-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f092/2447825/8f661d3efafc/1471-2172-9-32-6.jpg

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