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

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.