局部晚期宫颈癌放化疗后骨髓保留VMAT的动态免疫变化

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical and Translational Radiation Oncology Pub Date : 2026-05-01 Epub Date: 2026-01-16 DOI:10.1016/j.ctro.2026.101107

Anouk Corbeau , Marij J.P. Welters , Sanne Boekestijn , Jan Willem M. Mens , Henrike Westerveld , Mila Donker , Laura A. Velema , Hélène van Meir , Mariëtte I.E. van Poelgeest , Judith R. Kroep , Ingrid A. Boere , Sander C. Kuipers , Jeremy Godart , Mischa S. Hoogeman , Hein Putter , Carien L. Creutzberg , Remi A. Nout , Sjoerd H. van der Burg , Stephanie M. de Boer

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引用次数: 0

摘要

背景：放化疗对局部晚期宫颈癌（LACC）患者具有免疫抑制作用。先进的外束放射治疗（EBRT）和骨髓保留（BMS）放射治疗技术都可能降低骨髓剂量，从而减少对免疫系统的影响。在这项研究中，评估了BMS体积调节电弧治疗（VMAT）后LACC女性血液中的免疫组成和功能变化，并探索性地与接受非BMS放疗（RT）的LACC女性历史队列进行了比较。方法根据恩布拉- ii方案（BMS VMAT）或46-52.5 Gy / 23-30次（非BMS RT）进行放化疗加近距离放疗。在规定的时间点采集用于免疫监测的血液样本。采用线性混合效应模型进行统计分析。结果分别有18例和11例女性接受了BMS VMAT和非BMS RT。虽然BMS VMAT使平均骨盆骨剂量降低8.1 Gy，但它并不能预防治疗引起的白细胞减少和淋巴细胞减少。放化疗主要是降低CD4+ T辅助细胞和B细胞，而CD8+ T细胞和自然杀伤细胞的频率不变。尽管T细胞具有持续的增殖能力，但T细胞对常见病原体的反应性降低，并且与调节性T细胞数量的增加相一致。激活免疫细胞的潜力保持不变，树突状细胞少量增加，髓源性抑制细胞减少，髓细胞呈递抗原和激活T细胞的能力保持不变。结论本研究揭示了LACC放化疗后的动态免疫变化。由于BMS VMAT发生免疫抑制，优化BMS和探索其他技术是必要的。

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Dynamic immune changes after bone marrow sparing VMAT in women with locally advanced cervical cancer treated with chemoradiotherapy

Background

Chemoradiotherapy is immunosuppressive in women with locally advanced cervical cancer (LACC). Both advanced external-beam radiation therapy (EBRT) and bone marrow sparing (BMS) radiotherapy techniques might lower bone marrow dose and therefore reduce the impact on the immune system. In this study, immune composition and function changes in the blood of women with LACC were evaluated for BMS volumetric-modulated arc therapy (VMAT) and exploratively compared with a historical cohort of women with LACC who underwent non-BMS radiotherapy (RT) with older EBRT techniques.

Methods

Women were treated with chemoradiotherapy followed by brachytherapy according to EMBRACE-II protocol (BMS VMAT) or with 46–52.5 Gy in 23–30 fractions (non-BMS RT). Blood samples for immunomonitoring were collected at set timepoints. Statistical analyses were performed using linear mixed-effects models.

Results

Eighteen and eleven women received BMS VMAT and non-BMS RT, respectively. Although BMS VMAT reduced mean pelvic bone dose by 8.1 Gy, it did not prevent treatment-induced leukopenia and lymphopenia. Chemoradiotherapy mainly reduced CD4+ T helper cells and B cells, leaving CD8+ T-cell and natural killer-cell frequencies untouched. T-cell reactivity to common pathogens was decreased, despite sustained T-cell proliferative capacity, and coincided with increased numbers of regulatory T cells. The potential to activate immune cells remained intact, with small increases in dendritic cells, decreases in myeloid-derived suppressor cells, and preserved capacity of myeloid cells to present antigen and activate T cells.

Conclusion

Our study provided insight in the dynamic immune changes following chemoradiotherapy in LACC. As immunosuppression occurred with BMS VMAT, optimizing BMS and exploring other techniques is warranted.

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