Background: Endometrial cancer is one of the most common female genital cancers and poses a significant clinical problem due to its increasing incidence and variable prognosis depending on the stage of the disease. The development of EC is largely dependent on interactions with the immune system, including immune checkpoints (ICPs) such as PD-1, PD-L1, and PD-L2. The aim of our study was to evaluate the PD-1/PD-L1/PD-L2 pathway in EC and its clinical significance.Methods: The analysis was performed by flow cytometry on myeloid and plasmacytoid dendritic cells and monocytes (MO) in peripheral blood (PB). The concentration of sPD-1, sPD-L1, and sPD-L2 in plasma was determined by ELISA. Additionally,PD-L1andPD-L2gene expression levels in tumor tissue (TT) were assessed using real-time polymerase chain reaction (qPCR). The obtained results were correlated with clinical data of EC patients.Results: Patients with EC had lower percentages of PD-L1-positive MO and pDCs, as well as PD-L2-positive MO and mDCs, compared with the control group. We observed accumulation of sPD-1 and lower levels of sPD-L1 and sPD-L2 in EC patients compared to the control group, with sPD-L2 correlating withPD-L2gene expression level in the TT.Conclusions: The study results indicate a difference in the distribution of mDCs, pDCs, and MO with PD-L1/PD-L2 expression in EC patients. Reduced percentages of MO and DCs expressing PD-L1 and PD-L2, altered concentrations of soluble forms of these IPCs, and correlations with gene expression in TT suggest that dysregulation of this pathway may influence disease progression. Furthermore, the relationships between immunological parameters and clinical features such as BMI and FIGO stages suggest the potential use of these factors as diagnostic and prognostic biomarkers and the possibility of incorporating them into future therapeutic strategies. However, further studies are necessary to validate this hypothesis.
背景:子宫内膜癌是最常见的女性生殖系统恶性肿瘤之一,其发病率持续上升且预后因疾病分期而异,已成为重要的临床问题。该疾病的发展在很大程度上依赖于与免疫系统的相互作用,包括PD-1、PD-L1和PD-L2等免疫检查点。本研究旨在评估子宫内膜癌中PD-1/PD-L1/PD-L2通路及其临床意义。 方法:通过流式细胞术分析外周血中髓样树突状细胞、浆细胞样树突状细胞及单核细胞的表型特征。采用酶联免疫吸附法测定血浆中可溶性PD-1、PD-L1和PD-L2的浓度。同时,通过实时荧光定量聚合酶链反应检测肿瘤组织中PD-L1和PD-L2的基因表达水平。将所得结果与子宫内膜癌患者的临床资料进行相关性分析。 结果:与对照组相比,子宫内膜癌患者PD-L1阳性单核细胞与浆细胞样树突状细胞、PD-L2阳性单核细胞与髓样树突状细胞的百分比均显著降低。研究观察到患者血浆中可溶性PD-1积累,而可溶性PD-L1和PD-L2水平降低,其中可溶性PD-L2水平与肿瘤组织中PD-L2基因表达呈正相关。 结论:研究结果表明子宫内膜癌患者表达PD-L1/PD-L2的髓样树突状细胞、浆细胞样树突状细胞及单核细胞的分布存在异常。表达PD-L1和PD-L2的单核细胞与树突状细胞比例降低、可溶性免疫检查点分子浓度改变及其与肿瘤组织基因表达的相关性,提示该通路失调可能影响疾病进展。此外,免疫学参数与体质指数、国际妇产科联盟分期等临床特征的相关性表明,这些指标有望成为诊断和预后的生物标志物,并可能应用于未来治疗策略。但该假设仍需进一步研究验证。