Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

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.