The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer.
The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer.
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DOI：
10.1038/sj.bjc.6604963
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发表时间：
2009-04-07
影响因子：
8.8
通讯作者：
Stebbing, J.
中科院分区：
文献类型：
--
作者：
Horlock, C.;Stott, B.;Dyson, P. J.;Morishita, M.;Coombes, R. C.;Savage, P.;Stebbing, J.
除了对 HER2 阳性细胞的直接靶向作用外，曲妥珠单抗还可能具有调节乳腺癌患者细胞免疫系统活性的治疗作用。为了进一步研究这一点，我们对曲妥珠单抗治疗之前、期间和之后调节性 T (Treg)、Th17、自然杀伤 (NK) 和 NK T (NKT) 细胞的平衡进行了研究。在整个治疗过程中，测量了乳腺癌患者和正常对照组外周血中循环 Treg 细胞、Th17 细胞、NK 和 NKT 细胞的序列频率。乳腺癌个体外周血Treg频率显着高于健康对照者（9.2或8.6 vs 6%；P<0.05），而HER2阳性和HER2阴性个体之间Treg频率无显着差异。与健康对照和HER2阴性患者相比，HER2阳性患者的Th17细胞数量最低（0.31 vs 0.75%或0.84%；P=0.01）。在转移性乳腺癌（MBC）中，Treg 和 Th17 频率之间似乎存在负相关关系，曲妥珠单抗治疗期间 Treg 水平显着降低（P=0.04），而 Th17 频率同时增加（P=0.04）。这项研究支持了早期的数据，即与健康个体相比，乳腺癌患者中 Treg 细胞的出现频率更高。我们首次发现 HER2 阳性乳腺癌个体的循环 Th17 细胞数量减少，这似乎与 MBC 中 Treg 频率呈负相关。 Treg ：Th17 比例的平衡变化似乎表征了癌症状态，而且这种变化会被曲妥珠单抗治疗所破坏。
In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (Treg), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating Treg cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher Treg frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in Treg frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between Treg and Th17 frequencies in metastatic breast cancer (MBC) with Treg levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that Treg cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with Treg frequency in MBC. The change in balance of the Treg : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
8.8
作者：
Nedergaard BS;Ladekarl M;Thomsen HF;Nyengaard JR;Nielsen K
通讯作者：
Nielsen K
影响因子：
32.4
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
通讯作者：
Stockinger, B
影响因子：
5.8
作者：
Diederichsen, ACP;Hjelmborg, JV;Fenger, C
通讯作者：
Fenger, C
影响因子：
4.4
作者：
Kryczek, Ilona;Wei, Shuang;Zou, Weiping
通讯作者：
Zou, Weiping