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.

中文翻译：

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来自可手术乳腺癌患者的功能失调、无反应性、单核细胞衍生的树突细胞的体外恢复和激活：IFN-α的关键作用。

背景树突状细胞(DC)在启动有效的细胞介导的免疫反应中起关键作用，但在乳腺癌中是功能失调的和无反应性的。逆转这种功能障碍和建立最佳 DC 功能是诱导有效抗癌免疫反应的关键先决条件。结果 分别使用 4 种细胞因子条件培养基 (CCM) (GM-CSF) 从外周血单核细胞 (PBM) 和淋巴结单核细胞 (LNM) 的贴壁培养物中体外产生的外周血 DC (PBDC) 和淋巴结 DC (LNDC) +IL-4+TNF-α+IFN-α）或 3 CCM（GM-CSF+IL-4+TNF-α）在混合淋巴细胞 DC 反应（MLDCR，p < 0.001)，表达显着更高水平的 HLA-DR、CD86、与 2 CCM (GM-CSF+IL-4) 或单独培养基相比，从 PBM 和 LNM 产生的 DCs (p < 0.001)。与 PBDC 相比，用 3 个 CCM 或 4 个 CCM 生成的 PBDC 显示出显着（p < 0.001）增强的巨胞饮能力（葡聚糖颗粒）并诱导体外白细胞介素-12p40（IL-12p40）的产生和分泌增加（p < 0.001）仅使用 2 CCM 或培养基从单核细胞生成。与未用 LPS 刺激的对照 DC 相比，用 4 个 CCM 生成的 PBDC 的脂多糖 (LPS) 刺激表明 IL-6 的分泌增强，但 IL-12p70 的分泌没有增强（p < 0.001）。结论 来自可手术乳腺癌患者的功能障碍和无反应性 PBDC 和 LNDC 可以通过使用含有 IFN-α 的 4 CCM 的前体贴壁单核细胞的离体培养得到最佳逆转。在存在 IFN-α 的情况下，可以看到 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 PBDC 的 4 CCM 在体外不产生和分泌 IL-12p70。