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

Jintong Chen; Yunwei Zhang; Hua Zhang; Mingyue Zhang; He Dong; Tianxue Qin; Sujun Gao; Siqing Wang

doi:10.1016/j.isci.2023.107531

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

iScience. 2023 Aug 3;26(9):107531. doi: 10.1016/j.isci.2023.107531. eCollection 2023 Sep 15.

Authors

Jintong Chen¹, Yunwei Zhang², Hua Zhang³, Mingyue Zhang⁴, He Dong⁴, Tianxue Qin², Sujun Gao², Siqing Wang¹

Affiliations

¹ Department of Cancer Immunology, First Hospital of Jilin University, Changchun 130061, China.
² Department of Hematology, First Hospital of Jilin University, Changchun 130061, China.
³ Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, China.
⁴ Department of Gynecological Oncology, First Hospital of Jilin University, Changchun 130021, China.

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.

Keywords: Cancer; Components of the immune system; Immunology.