Elevated chronic inflammatory factors and myeloid-derived suppressor cells indicate poor prognosis in advanced melanoma patients
Elevated chronic inflammatory factors and myeloid-derived suppressor cells indicate poor prognosis in advanced melanoma patients
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DOI：
10.1002/ijc.29297
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发表时间：
2015-05-15
影响因子：
6.4
通讯作者：
Umansky, Viktor
中科院分区：
文献类型：
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作者：
Jiang, Huanhuan;Gebhardt, Christoffer;Umansky, Viktor
慢性炎症被认为是肿瘤发生和发展的标志之一。此外，炎症因子的长期产生和积累导致与癌症进展相关的局部和全身免疫抑制。然而，炎症介质，免疫抑制细胞和恶性黑色素瘤患者的临床结果之间的相关性研究很少。在这项研究中，我们进行了各种炎症因子，骨髓源性抑制细胞（MDSC）和调节性T细胞（TCFs）在不同阶段的恶性黑色素瘤患者的外周血中的复杂分析。我们证明，血清IL-1，IFN-γ和CXCL 10水平显着增加，在晚期黑色素瘤患者。此外，与年龄和性别匹配的健康供体相比，发现这些因素与MDSC和THBE的频率增加相关。重要的是，与疾病稳定的患者相比，具有进展迹象的晚期黑色素瘤患者显示出显著升高的IL-1和CXCL 10浓度。此外，循环单核细胞（Mo）-MDSC的富集与这些患者的无进展生存期降低显著相关。我们的数据突出了循环炎症介质、Mo-MDSC和临床结局之间的复杂关联，并表明它们在晚期黑色素瘤患者中的水平具有重要的预后价值，可以识别疾病进展高风险患者。肿瘤进展可由慢性炎症驱动，慢性炎症诱导局部和全身免疫抑制。在这项黑色素瘤患者的研究中，作者将循环炎症因子、髓源性抑制细胞（MDSC）和调节性T细胞（TCFs）与临床结局相关联。晚期黑色素瘤患者显示IL-1b、IFN-g、CXCL 10、单核细胞MDSC（Mo-MDSC）和TcR的积聚。此外，IL-1b、CXCL 10和Mo-MDSC的增加与无进展生存期的降低相关，表明它们具有重要的预后作用。
Chronic inflammation is considered to be one of the hallmarks for tumor initiation and progression. Moreover, a long-term production and accumulation of inflammatory factors lead to a local and systemic immunosuppression associated with cancer progression. However, the correlation between inflammatory mediators, immunosuppressive cells and the clinical outcome of malignant melanoma patients was poorly investigated. In this study, we performed a complex analysis of various inflammatory factors, myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of patients suffering from malignant melanoma of different stages. We demonstrated that levels of serum IL-1, IFN- and CXCL10 were significantly increased in advanced melanoma patients. In addition, these factors were found to be associated with an increased frequency of MDSCs and Tregs as compared to age- and gender-matched healthy donors. Importantly, advanced melanoma patients with signs of progression displayed markedly elevated concentrations of IL-1 and CXCL10 as compared to patients with stable disease. Moreover, an enrichment of circulating monocytic (Mo)-MDSCs significantly correlated with a decreased progression free survival of these patients. Our data highlight a complex association between circulating inflammatory mediators, Mo-MDSCs and the clinical outcome as well as suggest that their levels in patients with advanced melanoma are of important prognostic value allowing the identification of those with high risk of disease progression.What's new? Tumor progression can be driven by chronic inflammation that induces local and systemic immunosuppression. In this study of melanoma patients, the authors correlated circulating inflammatory factors, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) with clinical outcome. Patients with advanced melanoma displayed an accumulation of IL-1b, IFN-g, CXCL10, monocytic MDSCs (Mo-MDSCs) and Tregs. Moreover, an increase in IL-1b, CXCL10 and Mo-MDSCs correlated with a decreased progression free survival, indicating their important prognostic role.