Interleukin-18 是细胞因子 IL- 1 家族的成员，在神经胶质瘤中表达上调。然而，其对神经胶质瘤的影响仍不清楚。本研究旨在探讨白细胞介素18表达在胶质瘤中的作用和潜在机制。在这里，我们证明 IL-18 通过增加培养的神经胶质瘤细胞的增殖和抑制细胞凋亡来增强对替莫唑胺的耐药性。进一步的体内研究表明，IL-18 促进荷瘤 BALB/c 裸鼠对替莫唑胺的耐药性。机械探索表明，IL-18刺激可以激活胶质瘤细胞中的PI3K/AKT信号通路，而PI3K抑制可以降低IL-18促进的替莫唑胺耐药。我们发现 IL-18 上调神经胶质瘤中 CD274 的表达，揭示了其对微环境的潜在影响。此外，我们建立了肿瘤异种移植模型并探讨了抗白细胞介素18单克隆抗体的治疗效果。靶向白细胞介素 18 可延长荷瘤小鼠的生存期并减弱 CD274 的表达。在荷瘤小鼠中，抗白细胞介素 18 和抗 PD-1 单克隆抗体的联合治疗在抑制肿瘤生长方面显示出比单独治疗更佳的效果。总的来说，这些数据表明，IL-18 通过 PI3K/Akt 激活促进神经胶质瘤细胞对替莫唑胺化疗耐药，并通过调节 CD274 建立免疫抑制环境。这项研究强调了 IL-18 在神经胶质瘤中的治疗价值。© 2024。作者。

Interleukin-18, a member of the interleukin - 1 family of cytokines, is upregulated in glioma. However, its effects on glioma remain unclear. This study aimed to explore the role and underlying mechanisms of interleukin-18 expression in glioma. Here, we demonstrated that interleukin-18 enhanced resistance to temozolomide by increasing proliferation and inhibiting apoptosis in cultured glioma cells. Further in vivo studies revealed that interleukin-18 promoted temozolomide resistance in BALB/c nude mice bearing tumor. Mechanical exploration indicated that interleukin-18 stimulation could activate the PI3K/AKT signaling pathway in glioma cells, and PI3K inhibition could reduce the temozolomide resistance promoted by interleukin-18. We found that interleukin-18 upregulated CD274 expression in glioma, revealing its potential effects on the microenvironment. Furthermore, we established a tumor xenograft model and explored the therapeutic efficacy of anti-interleukin-18 monoclonal antibody. Targeting interleukin-18 prolonged survival and attenuated CD274 expression in the mice bearing tumor. Combined treatment with anti-interleukin-18 and anti-PD-1 monoclonal antibody showed better efficacy in suppressing tumor growth than either treatment alone in mice bearing tumor. Collectively, these data present that interleukin-18 promotes temozolomide chemoresistance in glioma cells via PI3K/Akt activation and establishes an immunosuppressive milieu by modulating CD274. This study highlights the therapeutic value of interleukin-18 in glioma.© 2024. The Author(s).