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宫颈癌患者中靶向免疫系统的近距离放疗

英文原题:Brachytherapy for targeting the immune system in cervical cancer patients.

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Brachytherapy for targeting the immune system in cervical cancer patients.

PubMed 2023/08/09(内容时间) BMC Immunol Q3 · IF 2.9(JCR 2025)

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研究概要

免疫生物标志物是宫颈癌重要的预测决定因素。较高的细胞毒性 NK 细胞和 Tregs 值较低的趋势可能支持使用 HDR-BT 而非 PDR-BT,并有助于开发与免疫治疗的有效联合方案。

研究思路结论见上方概要

基于标准治疗模式和免疫治疗的新联合方案需要了解传统治疗的免疫调节特性。目的是评估近距离放疗(BT)对宫颈癌免疫系统的影响,并确定最佳的靶向方式,即高剂量率近距离放疗(HDR-BT)与脉冲剂量率近距离放疗(PDR-BT)。

19例患者入组一项前瞻性研究,接受放化疗(CRT)并随后接受HDR-BT或PDR-BT。在CRT前、BT前以及BT后2周和4周采集外周血样本,通过流式细胞术进行免疫表型分析。采用Friedman单因素ANOVA、Conover事后检验和Wilcoxon符号秩检验比较不同时期细胞群的变化,进行多重两两比较,并评估治疗组(PDR和HDR)之间的差异。

NK 细胞(NKs)是BT的最佳靶点。接受HDR-BT的患者CD56dimCD16+ NK细胞的值显著更高、持续时间更长,且细胞毒性能力更强,而PDR-BT组则表现为CD56-CD16+ NK细胞的最高升高。此外,两种BT方式均与髓源性抑制细胞(MDSCs)的增加相关,而MDSCs与较差的临床预后相关。然而,在接受HDR-BT的患者中,CD4+CD25+Foxp3+CD45RA+调节性T细胞(Tregs)的百分比下降,尽管两种BT之间没有显著差异。

展开英文摘要原文

New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it.

Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR).

Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values ​​and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT.

Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy.

论文信息

作者
Linares I、Berenguer Frances MÁ、Cañas R、Najjari D、Gutiérrez C、Marín S、Comas S、Guedea F
单位
Radiation Oncology Department, Hospital Duran i Reynals, Institut Català d'Oncologia (ICO), Avinguda de la Gran Via de l'Hospitalet 199-203, L'Hospitalet de Llobregat, 08098, Barcelona, Spain. ilinaresgaliana@iconcologia.net.Spain
文献类型
非美国政府资助研究
期刊
BMC immunology2023 Aug 9
原文标识
PubMed 37559025 · DOI 10.1186/s12865-023-00559-y