Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk^∗MYC MM progression in a CD8⁺ T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses. Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM.

中文翻译：

---

IL-18失调是多发性骨髓瘤微环境中免疫抑制的关键驱动因素和可能的治疗靶标。

促进肿瘤的炎症和避免免疫破坏是癌症的标志。在这里，我们证明促炎性细胞因子白介素（IL）-18关键参与多发性骨髓瘤（MM）的这些标志。缺乏IL-18的小鼠在CD8 ^+中受到显着保护，免受Vk ^* MYC MM进展。T细胞依赖方式。MM小生境衍生的IL-18推动了髓样抑制细胞（MDSCs）的产生，从而加速了疾病的发展。对73例MM患者的免疫微环境进行全球转录组分析，强烈支持IL-18驱动的MDSC对T细胞反应的负面影响。令人惊讶的是，高水平的骨髓血浆IL-18与MM患者的总生存期差有关。此外，我们的临床前研究表明，IL-18可能是MM的潜在治疗靶标。