Preferential accumulation of regulatory T cells with highly immunosuppressive characteristics in breast tumor microenvironment.
Preferential accumulation of regulatory T cells with highly immunosuppressive characteristics in breast tumor microenvironment.
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DOI：
10.18632/oncotarget.16565
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发表时间：
2017-05-16
期刊：
影响因子：
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通讯作者：
Elkord E
中科院分区：
文献类型：
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作者：
Syed Khaja AS;Toor SM;El Salhat H;Faour I;Ul Haq N;Ali BR;Elkord E
免疫抑制细胞，如调节性T细胞(Tregs)在乳腺癌预后中的作用不明确，研究报告了Treg浸润与预后之间的正相关和负相关。这种差异可能是由于这些细胞中存在不同的免疫抑制分子。在目前的研究中，我们比较了原发性乳腺癌(PBC)患者周围正常组织和外周血中不同的Treg亚群在肿瘤微环境(TME)中的表现特征。我们报告，大多数肿瘤浸润性CD4+和CD8+T细胞具有CD39和PD-1表达所评估的终末穷尽表型。我们还表明，与正常组织相比，Tregs在乳房TME中积聚。Tregs的进一步鉴定表明，它们主要是FoxP3+Helios+，并表达高水平的CTLA-4和PD-1。FoxP3+Helios+Treg亚群在不同免疫抑制分子共表达的情况下优先聚集，可能对乳腺癌的预后有负面影响。综上所述，我们的结果提示乳腺肿瘤细胞可能利用Tregs，以及涉及CD39、PD-1和CTLA-4分子的不同抑制途径，为其创造一个免疫颠覆的生存环境，对这些免疫抑制分子的双重阻断可能被认为是治疗乳腺癌的有效方法。
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients. We report that the majority of tumor-infiltrating CD4+ and CD8+ T cells have terminally exhaustive phenotype as assessed by CD39 and PD-1 expressions. We also show that Tregs are accumulated in breast TME compared to normal tissue. Further characterization of Tregs showed that these are mainly FoxP3+Helios+ and express high levels of CTLA-4 and PD-1. This preferential accumulation of FoxP3+Helios+ Treg subset with co-expression of different immune inhibitory molecules might have a negative effect on breast cancer prognosis. Taken together, our results suggest that breast tumor cells might utilize Tregs, and different suppressive pathways involving CD39, PD-1 and CTLA-4 molecules in creating an immune-subversive environment for them to survive, and a dual blockade of these immunosuppressive molecules might be considered as an effective method in breast cancer treatment.