Chen Jintong, Zhang Yunwei, Zhang Hua, Zhang Mingyue, Dong He, Qin Tianxue, Gao Sujun, Wang Siqing
Department of Cancer Immunology, First Hospital of Jilin University, Changchun 130061, China.
Department of Hematology, First Hospital of Jilin University, Changchun 130061, China.
iScience. 2023 Aug 3;26(9):107531. doi: 10.1016/j.isci.2023.107531. eCollection 2023 Sep 15.
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.
Th9细胞是癌症免疫治疗中强大的效应T细胞。然而，Th9细胞潜在的抗肿瘤机制仍需进一步阐明。在此，我们表明Th9细胞不仅高水平表达IL-9，还表达IL-24。我们发现敲除Th9细胞中的 基因可促进Th9细胞增殖，但降低Th9细胞存活率 ，并且 。有趣的是，敲除Th9细胞中的 基因会降低Th9细胞的肿瘤特异性细胞毒性 。此外，在小鼠肿瘤模型中，用敲除 的Th9细胞进行免疫治疗比常规Th9细胞表现出更少的肿瘤抑制作用。我们发现用特异性抑制剂抑制Foxo1可下调Th9细胞中IL-24的表达并降低Th9细胞的抗肿瘤功效 。我们的结果确定IL-24是Th9细胞强大的抗肿瘤效应因子，并为Th9细胞介导的肿瘤治疗提供了一个靶点。 （注：原文中部分基因名称未明确写出，用 表示）
