Tumor secretion of CCL22 activates intratumoral Treg infiltration and is independent prognostic predictor of breast cancer.
Tumor secretion of CCL22 activates intratumoral Treg infiltration and is independent prognostic predictor of breast cancer.
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CCL22 的肿瘤分泌激活瘤内 Treg 浸润，是乳腺癌的独立预后预测因子
DOI：
10.1371/journal.pone.0076379
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fu L
中科院分区：
文献类型：
--
作者：
Li YQ;Liu FF;Zhang XM;Guo XJ;Ren MJ;Fu L
已有研究表明，Foxp 3 + TcR（TcR）的高密度浸润是乳腺癌患者预后不良的独立因素。然而，激活Treg浸润的细胞因子是未知的。本研究旨在评估CCL 22和TGF-β1在这一级联反应中的作用及其对BC患者预后的意义。选取417例浸润性乳腺癌患者，采用免疫组化法检测CCL 22和TGF-β1的表达。经鉴定，肿瘤分泌的CCL 22与肿瘤内Treg浸润正相关（P<0.0001），但其与肿瘤周围淋巴聚集体的相关性未被证明是显著的（P=0.056）。此外，发现CCL 22表达与已知与患者不良预后相关的肿瘤组织学特征相关，包括高组织学分级（P<0.0001）、阴性ER（P<0.0001）、阴性PR（P=0.001）和HER 2扩增（P=0.028）。与肿瘤内Treg浸润相似，CCL 22肿瘤分泌与乳腺癌分子亚型的预后相关（P<0.0001）。单因素分析显示CCL 22是影响BC患者总生存期（OS）和无进展生存期（PFS）的独立预后因素（P<0.0001），多因素分析也证实了这一点（分别为P=0.011和P=0.010）。TGF-β1的表达与肿瘤床浸润的T淋巴细胞数和肿瘤周围的淋巴聚集呈正相关（分别为P=0.023和P=0.046），但与乳腺癌的分子亚型和患者的预后无关。我们的研究表明，CCL 22和TGF-β1都是肿瘤内Foxp 3 + TGF 3浸润的候选化学引诱物;然而，与后者不同，CCL 22是BC患者的独立预后预测因子，因此它可能作为BC免疫策略的靶点。
It has been reported that dense intratumoral infiltration of Foxp3 +Tregs (Tregs) was an independent factor for poor prognosis of breast cancer (BC) patients. However, the cytokines activating the Treg infiltration are not known. This study was undertaken to evaluate the role of CCL22 and TGF-β1 in this cascade and their prognostic significance for BC patients. 417 cases of invasive breast cancer were selected from the prior study cohort and the expressions of CCL22 and TGF-β1 were assessed by immunohistochemistry. It was identified that tumor secretion of CCL22 was positively correlated with the intratumoral Treg infiltration (P<0.0001), but its association with lymphoid aggregates surrounding the tumor was not proven to be significant (P=0.056). Moreover, CCL22 expression was found to be associated with the tumor histological features known to be related with unfavorable prognosis of patients, including high histological grade (P<0.0001), negative ER (P<0.0001), negative PR (P=0.001), and HER2 amplification (P=0.028). Similar to intratumoral Treg infiltrates, CCL22 tumor secretion correlated with the prognosis of the molecular subtypes of breast carcinoma (P<0.0001). Univariate analysis revealed CCL22 to be an independent prognostic factor for overall survival (OS, P<0.0001) and progression-free survival (PFS, P<0.0001) of BC patients that were confirmed by multivariate analysis (P=0.011 and P=0.010 respectively). In contrast, although TGF-β1 expression was positively correlated with both Tregs infiltrates into the tumor bed and lymphoid aggregates surrounding the tumor (P=0.023; P=0.046, respectively), its expression was not significantly associated with the molecular subtypes of breast carcinoma and the prognosis of the patients. Our study indicates that both CCL22 and TGF-β1 are candidate chemoattractants for intratumoral Foxp3 +Tregs infiltration; however, unlike the later, CCL22 is an independent prognostic predictor of BC patients, and it therefore may have the potential to serve as a target for immunotherapeutic strategy of BC.
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影响因子：
4.4
作者：
Miller, Ashley M.;Lundberg, Kajsa;Pisa, Pavel
通讯作者：
Pisa, Pavel
影响因子：
11.2
作者：
Faget, Julien;Biota, Cathy;Menetrier-Caux, Christine
通讯作者：
Menetrier-Caux, Christine
DOI：
10.1073/pnas.0408197102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Chen, ML;Pittet, MJ;Khazaie, K
通讯作者：
Khazaie, K
影响因子：
11.2
作者：
Gobert, Michael;Treilleux, Isabelle;Menetrier-Caux, Christine
通讯作者：
Menetrier-Caux, Christine
DOI：
10.1084/jem.190.10.1417
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bell D;Chomarat P;Broyles D;Netto G;Harb GM;Lebecque S;Valladeau J;Davoust J;Palucka KA;Banchereau J
通讯作者：
Banchereau J