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低剂量辐射疗法诱导外周血中疼痛和免疫调节的长期缓解——IMMO-LDRT01 试验的中期分析。

Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial.

机构信息

Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

出版信息

Front Immunol. 2021 Oct 12;12:740742. doi: 10.3389/fimmu.2021.740742. eCollection 2021.

Abstract

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients' pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.

摘要

低剂量辐射疗法(LDRT)治疗慢性炎症和退行性疾病具有广阔的前景,尤其适用于对经典疗法有抗药性的患者。LDRT 的目的是减轻患者的疼痛,提高他们的活动能力。尽管 LDRT 自 19 世纪末以来就已应用,但免疫机制仍不明确。在前瞻性 IMMO-LDRT01 试验(NCT02653079)中,分析了 LDRT 对患者外周血免疫状态、疼痛和生活质量的影响。在每次分割照射前和每次照射后,每次照射剂量为 0.5Gy,以及在随访时,都会抽取血液,以便通过多色流式细胞术确定详细的纵向免疫状态。在这里,我们报告了 125 名患者的中期分析结果,这些患者代表了计划招募患者的一半数量。LDRT 显著改善了患者的疼痛水平,并诱导了明显的全身免疫调节。虽然外周血中的白细胞总数保持不变,但 LDRT 诱导了嗜酸性粒细胞、嗜碱性粒细胞和浆细胞样树突状细胞的轻微减少,以及 B 细胞的增加。此外,LDRT 后激活的免疫细胞减少。特别是单核细胞系的细胞与 LDRT 诱导的临床症状改善相关,将这些免疫细胞作为治疗成功的预测生物标志物。我们得出结论,LDRT 通过诱导全身免疫调节来改善患者的疼痛,并且可以定义免疫生物标志物,以便在未来通过改善患者分层进行预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbc/8546320/4789c749aad0/fimmu-12-740742-g001.jpg

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