IL-24 is the key effector of Th9 cell-mediated tumor immunotherapy.

Th9 cells are powerful effector T cells for cancer immunotherapy. However, the underlying antitumor mechanism of Th9 cells still needs to be further elucidated. Here, we show that Th9 cells express high levels of not only IL-9, but also IL-24. We found that knockout of gene in Th9 cells promotes Th9 cell proliferation , but decreases Th9 cell survival and . Interestingly, knockout of gene in Th9 cells decreases the tumor-specific cytotoxicity of Th9 cells . In addition, immunotherapy with knockout Th9 cells exhibit less tumor inhibition than regular Th9 cells in mouse tumor models. We found that inhibition of Foxo1 by a specific inhibitor downregulates IL-24 expression in Th9 cells and decreases Th9 cell antitumor efficacy . Our results identify IL-24 as a powerful antitumor effector of Th9 cells and provide a target in Th9 cell-mediated tumor therapy.