期刊
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
卷 15, 期 13, 页码 5181-5186出版社
ASIAN PACIFIC ORGANIZATION CANCER PREVENTION
DOI: 10.7314/APJCP.2014.15.13.5181
关键词
Tumor-derived TGF-beta; shRNA; immune surveillance; Treg; MDSC
类别
资金
- National Science Foundation of China [31230025, 31170858, 31370883, 31000400]
- International S&T Cooperation Program of China [2010DFB3400]
- National Basic Research Grant of China [2010CB529100]
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 naive 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.
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