Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

  • Li, Zheng (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Zhang, Li-Juan (Tianjin Medical University) ;
  • Zhang, Hong-Ru (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Tian, Gao-Fei (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Tian, Jun (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Mao, Xiao-Li (Department of Immunology, School of Basic Medical Science, Wuhan University) ;
  • Jia, Zheng-Hu (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Meng, Zi-Yu (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Zhao, Li-Qing (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Yin, Zhi-Nan (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Wu, Zhen-Zhou (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University)
  • Published : 2014.07.15
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Abstract

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Keywords

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