由于治疗选择有限，复发性或转移性宫颈癌的 5 年生存率极低，约为 17%。 CDYL 作为癌基因或抑癌基因，在多种癌症的发展中发挥着关键作用，且具有背景依赖性。然而，CDYL在宫颈癌发生中的作用尚未被探索。在宫颈癌和细胞系中检测了CDYL的表达。通过功能获得实验检测CDYL/IRF2BP2/PD-L1轴对宫颈癌细胞恶性表型的影响。我们开发了宫颈癌小鼠模型来验证体外结果。临床数据分析表明，CDYL 表达下调，与宫颈癌患者的不良预后相关。 CDYL 过表达可抑制宫颈癌细胞的增殖和侵袭，并通过降低 PD-L1 表达和逆转肿瘤免疫抑制微环境来增强免疫反应。从机制上讲，CDYL 通过转录抑制宫颈癌细胞中的 IRF2BP2 来抑制 PD-L1 表达。总之，我们的研究结果证实了 CDYL 在宫颈癌发生和免疫检查点阻断治疗敏感性中的关键作用，并支持 CDYL 可能是一种潜在的假设宫颈癌患者的新型免疫治疗反应预测生物标志物。版权所有 © 2024。由 Elsevier Inc. 出版。

Recurrent or metastatic cervical cancer have an extremely low 5-year survival rates about 17% due to limited therapeutic options. CDYL plays a critical role in multiple cancer development, as an oncogene or tumor suppressor in a context-dependent manner. However, the role of CDYL in cervical carcinogenesis has not yet been explored.CDYL expression was examined in cervical cancer and cell lines. The effect of CDYL/IRF2BP2/PD-L1 axis on malignant phenotypes of cervical cancer cells were tested with gain-of-function experiments. A mouse model of cervical cancer was developed to validate the in vitro results.Clinical data analysis revealed that CDYL was downregulated and associated with a poor prognosis in cervical cancer patients. CDYL overexpression suppressed cervical cancer cells proliferation and invasion in vitro and vivo assays and enhanced the immune response by decreasing PD-L1 expression and reversing the tumor immunosuppressing microenvironment. Mechanistically, CDYL inhibited the PD-L1 expression through transcriptionally suppressing IRF2BP2 in cervical cancer cells.Taken together, our findings established the crucial role of CDYL in cervical carcinogenesis and sensitivity for immune checkpoint blockade therapy, and supported the hypothesis that CDYL could be a potential novel immunotherapy response predictive biomarker for cervical cancer patients.Copyright © 2024. Published by Elsevier Inc.