Role of plasmacytoid dendritic cells and inducible costimulator-positive regulatory T cells in the immunosuppression microenvironment of gastric cancer.

Role of plasmacytoid dendritic cells and inducible costimulator-positive regulatory T cells in the immunosuppression microenvironment of gastric cancer.
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浆细胞样树突状细胞和诱导共刺激物阳性调节性T细胞在胃癌免疫抑制微环境中的作用

DOI:
10.1111/cas.12327
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发表时间:
2014-02
期刊:
影响因子:
5.7
通讯作者:
Yu JR
Yu JR
中科院分区:
医学2区
文献类型:
--
作者:
Huang XM;Liu XS;Lin XK;Yu H;Sun JY;Liu XK;Chen C;Jin HL;Zhang GE;Shi XX;Zhang Q;Yu JR

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调节性T细胞(Tregs)和浆细胞样树突状细胞(pDCs)在癌症的免疫逃逸中发挥重要作用。本研究通过流式细胞术研究了胃癌(GC)患者和健康供者外周血中pDCs和pDCs诱导的诱导共刺激物(ICOS)+ Treg群体。免疫组化法检测这些细胞在癌组织、瘤周组织和正常胃黏膜中的分布。同时测定血浆和组织中白细胞介素-10、转化生长因子-β1等细胞因子的浓度。我们发现,与健康供者相比,GC患者外周血中pDCs、Tregs和ICOS+ Tregs的数量增加。在组织中,Tregs和ICOS+ Tregs主要分布于癌组织,而pDCs主要分布于瘤周组织。癌组织和瘤周组织中Foxp3+ICOS+/Foxp3+细胞比例高于正常组织。晚期胃癌患者肿瘤及瘤周组织中ICOS+ Tregs较多。GC患者外周血及瘤周组织中pccs与ICOS+ Tregs呈正相关。综上所述,pDCs可能在募集ICOS+ Tregs中发挥潜在作用,并且都参与了GC的免疫抑制微环境。
Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)+ Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-β1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS+ Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS+ Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3+ICOS+/Foxp3+ cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS+ Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS+ Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS+ Tregs, and both participate in the immunosuppression microenvironment of GC.
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