Increased number of intratumoral IL-17+cells, a harbinger of the adverse prognosis of triple-negative breast cancer
Increased number of intratumoral IL-17+cells, a harbinger of the adverse prognosis of triple-negative breast cancer
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瘤内IL-17细胞数量增加，是三阴性乳腺癌不良预后的预兆
DOI：
10.1007/s10549-020-05540-6
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发表时间：
2020-01-29
影响因子：
3.8
通讯作者：
Guo, Xiao-Jing
中科院分区：
文献类型：
--
作者：
Qian, Xiao-Long;Xu, Peng;Guo, Xiao-Jing
三阴性乳腺癌（TNBC）是一种侵袭性癌症亚型，缺乏有效的靶向治疗。白细胞介素17（IL-17）是肿瘤微环境中分泌的一个细胞因子家族，通过多种分子途径影响肿瘤的进展。到目前为止，它在TNBC中的作用仍然很少探索。材料与方法采用免疫组化方法检测IL-17+细胞在无特殊类型特征的TNBC中的分布、与肿瘤微血管生成的关系以及对患者预后的影响。结果与具有三阴性分子特征的髓样癌（TNBC-MC）相比，我们发现TNBC-NST的瘤内基质和瘤外基质中IL-17+细胞浸润显著增加。类似地，在TNBC-NST和TNBC-MC两者中的瘤内和瘤外基质中注意到具有⑶ 4和IL-17共表达的基质细胞。此外，肿瘤内IL-17+细胞与血管内皮生长因子A（VEGFA）的肿瘤细胞表达和肿瘤内肿瘤微血管密度（MVD）呈正相关。多因素分析显示，肿瘤内IL-17+细胞（P = 0.018）、MVD（P = 0.039）和TNM分期（P = 0.002）是预测PFS不良的独立预后因素。结论IL-17在TNBC NST瘤内基质细胞中呈高表达。IL-17的过表达可能通过其信号转导途径参与活跃的肿瘤微血管生成，导致肿瘤分泌VEGFA增加，进而促进肿瘤的进展。IL-17可作为TNBC NST患者个体化治疗的新靶点。进一步的研究被认为是进一步探索IL-17+基质细胞在乳腺癌中的作用。
Introduction Triple negative breast cancer (TNBC) is an aggressive cancer subtype and lack of effective targeted therapies. It has been recently reported that Interleukin 17 (IL-17), a family of cytokines secreted in tumor microenvironment, affects tumor progression through a variety of molecular pathways. Its role in TNBC is so far still poorly explored. Materials and methods We employed immunohistochemistry to evaluate the distribution of IL-17+ cells in TNBC with no special type features (TNBC-NST), their association with tumor microangiogenesis, as well as their impact on prognosis of the patients. Results In comparison to medullary carcinoma with triple-negative molecular features (TNBC-MC), we found a significant increase in IL-17+ cell infiltrates in intratumoral stroma and extratumoral stroma of TNBC-NST. Similarly, stromal cells with co-expression of CD4 and IL-17 were noted in intratumoral and extratumoral stroma in both TNBC-NST and TNBC-MC. In addition, intratumoral IL-17+ cells were positively associated with tumor cell expression of vascular endothelial growth factor A (VEGFA) and with intratumoral tumor microvascular density (MVD). Multivariate analysis identified that intratumoral IL-17+ cells (P = 0.018), MVD (P = 0.039), and TNM stage (P = 0.002) were independent prognostic factors for predicting poor PFS. Conclusion The study indicates that IL-17 is overexpressed in intratumoral stromal cells of TNBC-NST. The overexpression of IL-17 might engage in active tumor microangiogenesis through its signal transduction pathways resulting in increased tumor secretion of VEGFA, and then promote tumor progression. IL-17 might serve as a potential new target for individualized therapy to TNBC-NST patients by development of specific antibodies. Additional study is deemed to further explore the role of IL-17+ stromal cells in breast cancer.