Tumor-derived transforming growth factor-ß is critical for tumor progression and evasion from immune surveillance.
Asian Pac J Cancer Prev
; 15(13): 5181-6, 2014.
Article
en En
| MEDLINE
| ID: mdl-25040972
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-ß(TGF-ß) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-ß produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-ß in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-ß 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-ß also significantly reduced the conversion of naive CD4+ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-ß 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-ß is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-ß may serve as a potential therapeutic approach for cancer.
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Bases de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Neoplasias
Tipo de estudio:
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Asian Pac J Cancer Prev
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article