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

• Published in: Cancer science 2014-02, Vol.105 (2), p.150-158
• Main Authors: Huang, Xiao‐Mei, Liu, Xiao‐Sun, Lin, Xian‐Ke, Yu, Hang, Sun, Jian‐Yi, Liu, Xiao‐Kun, Chen, Chao, Jin, Hai‐Long, Zhang, Ge‐Er, Shi, Xiao‐Xiao, Zhang, Qing, Yu, Ji‐Ren
• Format: Article
• Language: English
• Subjects: Age; Antigens; Cancer therapies; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chemotherapy; Dendritic cells; Dendritic Cells - immunology; Female; Flow cytometry; Foxp3 protein; Gastric cancer; Gastric mucosa; Humans; immune defense suppression; Immune Tolerance - immunology; Immunohistochemistry; Immunology; Immunoregulation; Immunosuppression; Inducible T-Cell Co-Stimulator Protein - immunology; Interferon-alpha - immunology; Interleukin-10 - immunology; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Metastasis; Middle Aged; Original; Ovarian cancer; Patients; Peripheral blood; regulatory T cells; stomach neoplasms; Stomach Neoplasms - immunology; Stomach Neoplasms - pathology; T-Lymphocytes, Regulatory - immunology; Transforming growth factor; tumor escape; Tumor Microenvironment - immunology
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12327

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. We found that 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, while pDCs mainly in peritumor tissue. Both pDCs and ICOS+ Tregs participate in the immunosuppression microenviroment of gastric cancer together.