Department of Gastrointestinal Surgery, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China.
Cancer Sci. 2014 Feb;105(2):150-8. doi: 10.1111/cas.12327. Epub 2014 Jan 4.
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.
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。在这项研究中,我们通过流式细胞术研究了胃癌(GC)患者和健康供体外周血中的 pDCs 和 pDC 诱导的可诱导共刺激分子(ICOS)(+)Treg 群体。通过免疫组织化学检测这些细胞在癌组织、肿瘤周围组织和正常胃黏膜中的分布。还测量了白细胞介素 10 和转化生长因子-β1 等细胞因子的血浆和组织浓度。我们发现 GC 患者外周血中的 pDCs、Tregs 和 ICOS(+)Tregs 数量较健康供体增加。在组织中,Tregs 和 ICOS(+)Tregs 主要分布在癌组织中,而 pDCs 主要分布在肿瘤周围组织中。此外,癌组织和肿瘤周围组织中 Foxp3(+)ICOS(+)/Foxp3(+)细胞的比例高于正常组织。晚期 GC 患者肿瘤和肿瘤周围组织中的 ICOS(+)Tregs 更多。GC 患者外周血和肿瘤周围组织中的 pDCs 与 ICOS(+)Tregs 之间存在正相关。总之,pDCs 可能在招募 ICOS(+)Tregs 中发挥潜在作用,两者均参与 GC 的免疫抑制微环境。