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宫颈癌患者免疫系统的近距离放射疗法。

Brachytherapy for targeting the immune system in cervical cancer patients.

机构信息

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.

Radiobiology and Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Avinguda de la Gran Via de l'Hospitalet 199-203, L'Hospitalet de Llobregat, 08098, Barcelona, Spain.

出版信息

BMC Immunol. 2023 Aug 9;24(1):23. doi: 10.1186/s12865-023-00559-y.

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

基于标准治疗方式和免疫疗法的新组合需要了解传统治疗的免疫调节特性。目的是评估近距离放射治疗(BT)对宫颈癌免疫系统的影响,并确定最佳治疗方式,高剂量率近距离放射治疗(HDR-BT)与脉冲剂量率近距离放射治疗(PDR-BT),以靶向治疗。

方法

19 名患者入组前瞻性研究,接受放化疗(CRT),随后接受 HDR-BT 或 PDR-BT。在 CRT、BT 之前以及 BT 后 2 周和 4 周时,通过流式细胞术获取外周血样本进行免疫表型分析。采用 Friedman 单向方差分析、Conover 事后检验和 Wilcoxon 符号秩检验比较不同时期细胞群的变化,进行多次两两比较,并评估治疗组(PDR 和 HDR)之间的差异。

结果

自然杀伤细胞(NK)是 BT 的最佳靶标。接受 HDR-BT 的患者获得了更高的值和更长时间的 CD56dimCD16+NK 细胞,其具有更强的细胞毒性,而 PDR-BT 组则表现出最高的 CD56-CD16+NK 细胞升高。此外,两种 BT 方式均与髓源性抑制细胞(MDSCs)的增加相关,与更差的临床预后相关。然而,接受 HDR-BT 的患者 CD4+CD25+Foxp3+CD45RA+调节性 T 细胞(Tregs)的百分比下降,尽管 BT 之间没有显著差异。

结论

免疫生物标志物是宫颈癌的重要预测决定因素。更高的细胞毒性 NK 细胞和 Tregs 值下降的趋势可能支持使用 HDR-BT 而不是 PDR-BT,并有助于与免疫疗法相结合开发有效的组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7134/10413692/879283db976e/12865_2023_559_Fig1_HTML.jpg

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