肺腺癌（LUAD）是肺癌最主要的组织学亚型，也是最致命的恶性肿瘤之一。 LUAD 的治疗需要确定新的治疗靶点。在这里，我们发现 MYC 相关的锌指蛋白 (MAZ) 在 LUAD 组织中上调。 MAZ 表达水平与患者存活率呈负相关。 MAZ 的沉默降低了肿瘤增殖以及促肿瘤趋化因子和半乳糖凝集素 9 (Gal-9)（一种免疫检查点分子）的表达。促肿瘤趋化因子和 Gal-9 分别通过募集骨髓细胞和抑制 T 细胞激活来诱导免疫抑制。从机制上讲，MAZ 转录调节 KRAS 表达并激活其下游 AKT-NF-κB 信号通路，这对于肿瘤进展和免疫逃避至关重要。此外，体内动物模型和生物信息学分析表明，MAZ 抑制可以增强免疫检查点阻断 (ICB) 治疗 LUAD 的疗效。总的来说，我们的结果表明 MAZ 通过 LUAD 中的 KRAS/AKT/NF-κB 信号传导在调节细胞增殖和免疫逃避中发挥重要作用。我们的研究结果为 LUAD 治疗提供了候选分子靶点，对提高 ICB 治疗的疗效具有重要意义。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Lung adenocarcinoma (LUAD) is the most dominant histological subtype of lung cancer and one of the most lethal malignancies. The identification of novel therapeutic targets is required for the treatment of LUAD. Here, we showed that MYC-associated zinc-finger protein (MAZ) is upregulated in LUAD tissues. MAZ expression levels are inversely correlated with patient survival. Silencing of MAZ decreased tumor proliferation and the expression of pro-tumorigenic chemokines and Galectin-9 (Gal-9), an immune checkpoint molecule. The pro-tumorigenic chemokines and Gal-9 induce immune suppression by recruitment of myeloid cells and inhibition of T cell activation, respectively. Mechanistically, MAZ transcriptionally regulates KRAS expression and activates its downstream AKT-NF-κB signaling pathway, which is crucial for tumor progression and immune evasion. Additionally, in vivo animal models and bioinformatic analyses indicated that MAZ suppression could enhance the efficacy of immune checkpoint blockade (ICB) therapy for LUAD. Overall, our results suggest that MAZ plays an important role in regulating cell proliferation and immune evasion via KRAS/AKT/NF-κB signaling in LUAD. Our findings offer a candidate molecular target for LUAD therapy, with implications for improving the efficacy of ICB therapy.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.