期刊
INTERNATIONAL JOURNAL OF CANCER
卷 127, 期 9, 页码 2129-2137出版社
WILEY
DOI: 10.1002/ijc.25238
关键词
T-bet; Th cell; IFN gamma; tumor development; metastatic melanoma
类别
资金
- National R&D Program for Cancer Control of National Cancer Center [0620380]
- MEST [R15-2006-020]
- Korea Health Promotion Institute [0620380] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据