TheRole Of Tumor-derived TGF-β In Evasion Of Tumor Immune Surveillance And Mechanism Of Tumor Induced Immune Tolerance In Liver

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance and inhibit anti-tumor immune responses. One of these mechanisms is to produceimmunosuppressive cytokines, such as TGF-β.TGF-β is a pleiotropic cytokine which plays important roles in cancer and immunoregulation. TGF-β produced by T cells has been demonstrated as an important factor for suppressing antitumor immune response, however, the role of tumor-derived TGF-β in this process is poorly understood.In this study, we used the method of RNAi to knockdown TGF-β expression in B16cells to investigate the effect of tumor-derived TGF-β on tumor progression and immune responses. Our results demonstrated that tumor-derived TGF-P promoted tumor formation, progression and metastasisin vivo. We revealed the possible underlying mechanisms that tumor-derived TGF-P could increase the number of MDSCs and CD4+Foxp3+Treg cells in the tumor environment, and inhibit IFN-y production by CTLs. Tumor-derived TGF-P also significantly reduced the conversion of naive CD4+T cells into Treg cells in vitro. Finally, we found that tumor-derived TGF-P suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provide evidence that tumor-derived TGF-P is a critical factor for tumor progression and evasion of the immune surveillance, and blocking tumor-derived TGF-P may serve as a potential therapeutic approach for cancer.The relationship between inflammation and cancer has been a worldwide problem which has got more and more attention. Lots of studies have shown that inflammation is a key factor during the progress of tumor. So we would like to know how the tumor can affect the immune system, and how it affects the inflammation of tumor-bearing host. Then we found a very interesting phenotype that B16tumor-bearing mice were highly resistant to ConA-induced acute hepatitis. Our results showed that the number of MDSCs and Tregs significantly increased in the liver of tumor-bearing mouse, as well as some cytokines, such as IL-6, IL-10and TGF-β. We demonstrated that MDSCs played a essential role in protecting the tumor-bearing mouse from ConA-induced acute hepatitis. The IFN-y produced by NKT cells, not CD4+T cells, in tumor-bearing mice was inhibited. Our results made some progress on better understanding the mechanisms of how tumor induce immune tolerance in liver, and may provide some basis for the immune therapy targeting the tumor induced immune tolerance.