title: Tumor-derived transforming growth factor-β is critical for tumor progression and evasion from immune surveillance.
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-β(TGF-β) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-β produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-β in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-β 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-γ production by CTLs. Knockdown of tumor-derived TGF-β also significantly reduced the conversion of naive CD4+ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-β 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-β is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-β may serve as a potential therapeutic approach for cancer.
authors.affiliation: State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China E-mail : naturepower@nankai.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Hong-Ru
authors.initials: HR
authors.lastname: Zhang
authors.forename: Gao-Fei
authors.initials: GF
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Mao
authors.forename: Zheng-Hu
authors.initials: ZH
authors.lastname: Jia
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Meng
authors.forename: Li-Qing
authors.initials: LQ
authors.lastname: Zhao
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Yin
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015166:Monitoring, Immunologic; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D007371:Interferon-gamma