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

Authors
Lee, KihyunMin, Hyun JungJang, Eun JungHong, Jeong-HoHwang, Eun Sook
Issue Date
1-Nov-2010
Publisher
WILEY
Keywords
T-bet; Th cell; IFN gamma; tumor development; metastatic melanoma
Citation
INTERNATIONAL JOURNAL OF CANCER, v.127, no.9, pp.2129 - 2137
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF CANCER
Volume
127
Number
9
Start Page
2129
End Page
2137
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/115345
DOI
10.1002/ijc.25238
ISSN
0020-7136
Abstract
T-box-containing protein expressed in T cells (T-bet) is a master transcription factor for the development of interferon (IFN) gamma-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 IFN gamma production in T cells and tumor cell apoptosis. Late induction of T-bet expression in tumor-bearing mice produced comparable amounts of IFN gamma 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.
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