宫颈癌患者PD-L1表达与免疫治疗疗效及免疫细胞的相关性研究
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张家口市卫生健康和生物医疗专项项目(2421098D)


Correlation between PD-L1 expression and efficacy of immunotherapy with immune cell profiles in cervical cancer patients
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    摘要:

    目的 探讨程序性细胞死亡配体1(PD-L1)表达在复发性或转移性宫颈癌患者中的临床意义及其与免疫细胞变化的关系。方法 选取2021年1月—2022年12月就诊于河北北方学院附属第一医院放射治疗科的患者121例。采用免疫组织检测PD-L1表达[综合阳性评分(CPS)],分为高表达组(CPS≥10)和低表达组(CPS<10);采用流式细胞术检测治疗前、治疗中和治疗后的免疫细胞[CD3+T、CD4+T、CD8+T、CD56+T和调节性T细胞(Tregs)]。主要评价指标为无进展生存期(PFS)。结果 PD-L1高表达率(CPS≥10)为35.54%,低表达率64.46%。PD-L1高表达与肿瘤转移及人乳头状瘤病毒(HPV)16/18感染均显著相关(均P<0.05)。PD-L1高表达组治疗前CD3+ T细胞、CD8+T细胞及Tregs比例显著高于低表达组(均P<0.001)。随访截止至2024年12月,PD-L1高表达组客观缓解率(ORR)(ORR=60.47% vs 38.46%,P=0.020)及PFS(中位PFS=26 vs 18个月,P<0.001)显著优于低表达组(P<0.05)。重复测量方差分析显示,PD-L1高表达组CD3+ T细胞(F=107.3,P<0.000 1)及CD8+ T细胞(F=407.7,P<0.000 1)水平随时间显著升高,且与时间存在交互作用(均P<0.05)。治疗中及治疗后,高表达组CD8+ T细胞较治疗前分别升高(均P<0.000 1),而低表达组无显著变化(P>0.05)。Tregs比例仅随时间下降(F=19.03,P<0.000 1),与PD-L1表达无关(P>0.05)。多因素Cox分析显示,PD-L1低表达及转移是PFS的独立危险因素(P<0.05)。结论 PD-L1高表达宫颈癌患者具有更强的CD8+ T细胞浸润及更低的Tregs比例,提示其免疫微环境更易被PD-1抑制剂激活,从而获得更优的近期疗效和PFS

    Abstract:

    Objective To investigate the clinical significance of PD-L1 expression and its relationship with dynamic changes in the immune microenvironment in patients with recurrent or metastatic cervical cancer. Methods A total of 121 patients treated at the Department of Radiotherapy, Hebei North University Affiliated First Hospital, from January 2021 to December 2022, were enrolled. PD-L1 expression was assessed by immunohistochemistry (combined positive score, CPS), categorized as high (CPS ≥10) or low (CPS<10). Immune cell subsets (CD3+ T, CD4+ T, CD8+ T, CD56+ T, and Tregs) were quantified via flow cytometry at baseline, during treatment, and post-treatment. The primary endpoint was progression-free survival (PFS). Results PD-L1 high expression (CPS≥10) and low expression (CPS<10) rates were 35.54% and 64.46%, respectively. High PD-L1 expression was significantly associated with metastasis and HPV16/18 infection (P<0.05). PD-L1 high-expression group exhibited significantly higher proportions of CD3+ T cells (65.95% vs.62.25%), CD8+ T cells (28.26% vs. 24.56%), and Tregs (5.58% vs.4.48%) compared to the low-expression group at pre-treatment (P <0.001). With follow-up until December 2024, the high PD-L1 group demonstrated superior objective response rate (ORR: 60.47% vs. 38.46%, P=0.020) and median PFS (26 vs.18 months, P<0.001). Repeated measures ANOVA revealed that CD3+ T cells (F =107.3, P<0.000 1) and CD8+ T cells (F=407.7,P<0.000 1) significantly increased over time in the high-expression group, with notable interaction effects between PD-L1 status and time (P<0.05). Post-treatment CD8V+ T cell levels in the high-expression group significantly rose during and after therapy (P<0.000 1), whereas no significant changes were observed in the low-expression group. Tregs decreased over time (F=19.03, P<0.000 1), independent of PD-L1 expression. Multivariate Cox analysis identified low PD-L1 expression (HR=1.771, P<0.05) and metastasis (HR=1.770, P<0.05) as independent risk factors for PFS.Conclusion High PD-L1 expression correlates with enhanced CD8+ T cell infiltration and reduced Treg proportions, suggesting a more responsive immune microenvironment to PD-1 inhibitors, leading to improved short-term outcomes and prolonged PFS

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  • 在线发布日期: 2026-06-18
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