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In vivo tumor suppression activity by T cell-specific T-bet restoration

Title
In vivo tumor suppression activity by T cell-specific T-bet restoration
Authors
Lee K.Min H.J.Jang E.J.Hong J.-H.Hwang E.S.
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2010
Journal Title
International Journal of Cancer
ISSN
0020-7136JCR Link
Citation
International Journal of Cancer vol. 127, no. 9, pp. 2129 - 2137
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
T-box-containing protein expressed in T cells (T-bet) is a master transcription factor for the development of interferon (IFN) γ-producing T helper 1 (Th1) cells and also functions in other immune cells including natural killer (NK), cytotoxic T lymphocytes and dendritic cells. T-bet-deficient mice increased susceptibility to viral infection and tumor development due to the defective functions of immune cells. T-bet is known to play a key role in NK-mediated antimetastatic response; however, it remains to be characterized whether T-bet is essential for in vivo tumor suppression mediated by T cells. Here, we have investigated in vivo tumor suppression effect of T-bet-restored T cells using T cell-specific and inducible T-bet transgenic mice generated in a T-bet-deficient background. T-bet-null mice increased susceptibility to tumor development, whereas induction of T cell-specific T-bet expression upon melanoma cell injection substantially suppressed tumor development by inducing IFNγ production in T cells and tumor cell apoptosis. Late induction of T-bet expression in tumor-bearing mice produced comparable amounts of IFNγ with control and significantly decreased tumor volume. In addition, increased melanoma lung metastasis in T-bet-deficient mice was strikingly inhibited by T-bet restoration in T cells. Intravenous injection of activated Th1 cells, not T-bet-null Th1 cells, attenuated metastatic melanoma progression, in addition, restoration of T-bet in T-bet-null Th1 cells certainly retrieved antimetastatic activity. These results suggest that T-bet expression in T cells is crucial for the control of tumor development and antimetastatic activity. © 2010 UICC.
DOI
10.1002/ijc.25238
Appears in Collections:
약학대학 > 약학과 > Journal papers
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