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 Il24 gene in Th9 cells promotes Th9 cell proliferation in vitro, but decreases Th9 cell survival in vitro and in vivo. Interestingly, knockout of Il24 gene in Th9 cells decreases the tumor-specific cytotoxicity of Th9 cells in vitro. In addition, immunotherapy with Il24 knockout Th9 cells exhibit less tu-mor inhibition than regular Th9 cells in mouse tumor models. We found that inhi-bition of Foxo1 by a specific inhibitor downregulates IL-24 expression in Th9 cells and decreases Th9 cell antitumor efficacy in vivo. Our results identify IL-24 as a powerful antitumor effector of Th9 cells and provide a target in Th9 cell-mediated tumor therapy.

Automated summary

Th9 cells express both IL-9 and IL-24, and knockout of the Il24 gene promotes cell proliferation but decreases cell survival. Knockout of Il24 gene also decreases the tumor-specific cytotoxicity of Th9 cells. Immunotherapy with Il24 knockout Th9 cells exhibits less tumor inhibition, while inhibition of Foxo1 decreases IL-24 expression and antitumor efficacy of Th9 cells.