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

Kihyun Lee, Hyun Jung Min, Eun Jung Jang, Jeong-Ho Hong, Eun Sook Hwang

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2129-2137
Number of pages9
JournalInternational Journal of Cancer
Volume127
Issue number9
DOIs
Publication statusPublished - 2010 Nov 1

Keywords

  • IFNγ
  • metastatic melanoma
  • T-bet
  • Th cell
  • tumor development

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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