METHODS: 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.
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.
CONCLUSIONS: 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.
方法:在宫颈癌和细胞系中检测CDYL的表达。通过功能获得实验测试CDYL/IRF2BP2/PD-L1轴对宫颈癌细胞恶性表型的影响。开发了宫颈癌小鼠模型以验证体外结果。
结果:临床数据分析显示CDYL下调并与宫颈癌患者的不良预后相关。CDYL过表达在体外和体内实验中抑制了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应答。机械上,CDYL通过转录抑制IRF2BP2在宫颈癌细胞中抑制PD-L1的表达。
结论:综合来看,我们的研究结果确定了CDYL在宫颈癌发生中的关键作用和免疫检查点阻断治疗的敏感性,并支持以下假设:CDYL可能是宫颈癌患者潜在的新型免疫疗法反应预测生物标志物。