Cross-talk between T cells and innate immune cells is crucial for IFN-gamma-dependent tumor rejection.

Though the importance of IFN-gamma in tumor immunity has been well-demonstrated, little is known about its source and how it is induced. By using various bone marrow chimeric mice, we show here that IFN-gamma essential for tumor immunity is solely produced by hemopoietic cells. Surprisingly, IFN-gamma derived from T cells was not necessary for tumor immunity in this model. In the immunized mice, in which only innate immune cells have the IFN-gamma-producing potential, tumors were efficiently rejected. The innate immune cells, such as NK1.1(+) cells and CD11b(+) cells, can provide sufficient amounts of IFN-gamma which requires, however, the help of T cells. The close cooperation between T cells and innate immune cells during tumor regression is likely mediated by IL-2. Together, our results clearly illustrate how T cells cooperate with innate immune cells for IFN-gamma-mediated tumor rejection and this may have important indications for clinical trials of tumor immunotherapy.