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

ABSTRACT: 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 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 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.

SUBMITTER: Chen J

PROVIDER: S-EPMC10480301 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Chen Jintong J Zhang Yunwei Y Zhang Hua H Zhang Mingyue M Dong He H Qin Tianxue T Gao Sujun S Wang Siqing S

iScience 20230803 9

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-specif ...[more]

PMID: 37680459

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Itk is required for Th9 differentiation via TCR-mediated induction of IL-2 and IRF4.

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IL-4 together with IL-1β induces antitumor Th9 cell differentiation in the absence of TGF-β signaling.

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| S-EPMC11015030 | biostudies-literature

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