Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
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DOI：
10.1186/s12967-016-0905-x
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发表时间：
2016-05-28
影响因子：
7.4
通讯作者：
Pawelec, Graham
中科院分区：
文献类型：
--
作者：
Bailur, Jithendra Kini;Gueckel, Brigitte;Pawelec, Graham
背景资料：识别血液中的免疫标记物，为乳腺癌患者的生存提供信息，不仅对预后有用，而且还可能提供促进生存过程的机制见解。方法：我们对循环浆细胞样树突状细胞（pDC）进行了表型分析，骨髓源性抑制细胞（MDSC）和调节性T细胞与75例未经治疗的乳腺癌患者28- 29例中T细胞对Her-2的体外应答相关结果：晚期肿瘤患者的循环pDC水平较低（p = 0.008）。5年生存率与高于中位循环pDC水平呈正相关（p = 0.03）。我们证实，在这个年轻和老年患者队列中，5年生存率与CD 8 + T细胞对Her-2肽的反应性相关，而与CD 4 + T细胞对Her-2肽的反应性无关（p = 0.04）。在先前建立的参数的分析中包括pDC揭示了具有对Her-2的CD 8 + T细胞应答以及MDSC：pDC的低比率的患者具有100%的5年存活率。高水平的pDCs和存在的CD 8 + T细胞对Her-2的反应是独立的阳性生存指标，根据多变量考克斯analysis.Conclusions：我们的新研究结果表明，循环pDCs可能是一个积极的预后指标，在乳腺癌患者的所有年龄段，连同以前建立的CD 8 + T细胞对Her-2抗原的反应，在老年患者只。这两个预后指标是独立的，强调了免疫在确保乳腺癌患者生存方面的重要作用，即使在那些没有接受免疫治疗的患者中也是如此。
Background: Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival.Methods: We phenotyped circulating plasmacytoid dendritic cells (pDCs), myeloid-derived suppressor cells (MDSCs) and regulatory T-cells in relation to T-cell responses to Her-2 in vitro in 75 untreated breast cancer patients 28-87 years of age at diagnosis.Results: Patients with later stage tumors had lower levels of circulating pDCs (p = 0.008). There was a positive association between 5-year survival and higher than median levels of circulating pDCs (p = 0.03). We confirmed that 5-year survival correlated with CD8+ but not CD4+ T-cell responsiveness to Her-2 peptides in this cohort of younger and older patients (p = 0.04). Including pDCs in the analysis of previously-established parameters revealed that patients who had a CD8+ T-cell response to Her-2 together with a low ratio of MDSCs: pDCs had 100 % 5-year survival. High levels of pDCs and the presence of a CD8+ T-cell response to Her-2 were independent positive survival indicators according to multivariate Cox analysis.Conclusions: Our new results suggest that circulating pDCs could be a positive prognostic indicator in breast cancer patients of all ages, together with the previously established CD8+ T-cell reactivity to Her-2 antigens in older patients only. These two prognostic indicators were independent and emphasize the important role of immunity in ensuring breast cancer patient survival, even in those not undergoing immunotherapy.