Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor
Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor
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DOI：
10.1002/eji.201242951
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发表时间：
2013-06-01
影响因子：
5.4
通讯作者：
Silva, Joao S.
中科院分区：
文献类型：
--
作者：
Benevides, Luciana;Cardoso, Cristina R. B.;Silva, Joao S.
乳腺癌是全世界妇女肿瘤相关死亡的主要原因。调节性T细胞（Treg）和Th 17细胞在一些肿瘤中富集，但这些细胞在乳腺浸润性导管癌（IDC）中的作用尚不清楚。我们发现，来自PBMC和肿瘤的CD 25（+）CD 4（+）T细胞表达高水平的Foxp 3、GITR、CTLA-4和CD 103，表明肿瘤浸润性Treg细胞是功能性的，可能被CCL 22募集。此外，我们观察到Th 17相关分子（IL-17 A、RORC和CCR 6）和肿瘤浸润性CD 4（+）和CD 8（+）T淋巴细胞产生的IL-17 A的上调。在肿瘤内检测到的血管生成因子CXCL 8、MMP-2、MMP-9和血管内皮生长因子可能由IL-17诱导，并指示不良的疾病预后。IDC患者Treg和Th 17细胞同步升高，Foxp 3、IL-17 A和RORC表达呈正相关，且与肿瘤侵袭性相关。因此，Treg和Th 17细胞可以通过Treg细胞介导的效应T细胞应答的抑制来影响疾病进展，如从IDC患者的PBMC分离的T细胞增殖的减少和产生IL-17的Th 17对血管生成因子的诱导所示。对Treg/Th 17轴调控的理解可能会为侵袭性肿瘤的控制带来新的前景。
Breast cancer is a leading cause of neoplasia-associated death in women worldwide. Regulatory T (Treg) and Th17 cells are enriched within some tumors, but the role these cells play in invasive ductal carcinoma (IDC) of the breast is unknown. We show that CD25(+)CD4(+) T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4, and CD103, indicating that tumor-infiltrating Treg cells are functional and possibly recruited by CCL22. Additionally, we observed upregulation of Th17-related molecules (IL-17A, RORC, and CCR6) and IL-17A produced by tumor-infiltrating CD4(+) and CD8(+) T lymphocytes. The angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor are possibly induced by IL-17 and indicative of poor disease prognosis. Treg and Th17 cells were synchronically increased in IDC patients, with positive correlation between Foxp3, IL-17A, and RORC expression, and associated with tumor aggressiveness. Therefore, Treg and Th17 cells can affect disease progression by Treg-cell-mediated suppression of the effector T-cell response, as indicated by a decrease in the proliferation of T cells isolated from PBMCs of IDC patients and induction of angiogenic factors by IL-17-producing Th17. The understanding of regulation of the Treg/Th17 axis may result in novel perspectives for the control of invasive tumors.