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Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer

  • Original Article
  • Ovarian Cancer
  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

Transforming growth factor-1 (TGF-β1), vascular endothelial growth factor (VEGF), and interleukin-10 (IL-10) may be critical cytokines in the microenvironment of a tumor, playing roles in immune suppression. This study was conducted to elucidate the roles and immunosuppressive functions of these cytokines in epithelial ovarian cancer (EOC).

Methods

The expression levels of TGF-β1, VEGF and IL-10 in malignant tissue were evaluated by immune-histochemistry and compared with corresponding borderline, benign, and tumor-free tissues. Moreover, relationships among the levels of these cytokines and correlations between expression and the prognosis of EOC were analyzed by Pearson rank correlations and multi-factor Logistic regression. The roles of TGF-β1, VEGF, and IL-10 in the immunosuppressive microenvironment of ovarian cancer were studied through dendritic cell (DC) maturation and CD4+CD25+FoxP3+ Treg generation in vitro experiments.

Results

TGF-β1, VEGF, and IL-10 were expressed in 100%, 74.69%, and 54.96% of EOC patients, respectively. TGF-β1 was an independent prognostic factor for EOC. IL-10 was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β1 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-10 that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs.

Conclusions

TGF-β1, VEGF and IL-10 play important roles in EOC and can lead to frequent immune evasion events.

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Authors and Affiliations

  1. Gynecology Oncology Center, Peking University People’s Hospital, Beijing, 100044, China

    Chan-zhen Liu, Li Zhang, Xiao-hong Chang, Ye-xia Cheng, Hong-yan Cheng, Xue Ye, Tian-yun Fu, Jun Chen & Heng Cui

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  1. Chan-zhen Liu
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  2. Li Zhang
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  3. Xiao-hong Chang
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  4. Ye-xia Cheng
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  5. Hong-yan Cheng
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  7. Tian-yun Fu
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  8. Jun Chen
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  9. Heng Cui
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Corresponding author

Correspondence to Heng Cui.

Additional information

This study was supported by the Natural Science Foundation of China (No. 30872750) and the Natural Science Foundation of Beijing (No. 7092108).

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Liu, Cz., Zhang, L., Chang, Xh. et al. Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer. Chin. J. Cancer Res. 24, 130–137 (2012). https://doi.org/10.1007/s11670-012-0130-y

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