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诊断时的调节性T细胞作为预测新诊断多发性骨髓瘤高风险功能的潜在生物标志物。

Tregs at Diagnosis as a Potential Biomarker for Predicting High-Risk Functionality in Newly Diagnosed Multiple Myeloma.

作者信息

Zhou Qiaolin, Xu Fang, Wen Jingjing, Yue Jing, Zhang Ya, Du Lijun, Kou Kun, Su Jing, Liu Yiping, Liang Xiaogong

机构信息

Hematology Department, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.

出版信息

Cancer Med. 2025 Jun;14(11):e70980. doi: 10.1002/cam4.70980.

DOI:10.1002/cam4.70980
PMID:40458003
Abstract

OBJECTIVE

This study investigated the role of regulatory T cells (Tregs) in newly diagnosed multiple myeloma (NDMM) patients, particularly in relation to early relapse and prognosis.

METHODS

The analysis included clinical data from 70 NDMM patients, with Tregs measured at diagnosis. Early relapse was defined as relapse within 18 months (ER18), and posttransplant survival extending beyond 12 months. Functional high risk (FHR) was evaluated based on this criterion.

RESULTS

For the overall cohort, the median progression-free survival (PFS) and overall survival (OS) were not reached, but in the ER18 cohort, median OS was 24.8 months and median PFS was 10.8 months. Key factors linked to early relapse included elevated serum creatinine levels (> 156 μmol/L), presence of extramedullary disease, and lower percentage of Tregs at diagnosis. Multivariate analysis revealed that extramedullary disease and lower percentage of Tregs were significant predictors of early relapse. Factors such as age, elevated creatinine, extramedullary disease, and lower percentage of Tregs were associated with poorer PFS. Further analysis confirmed that extramedullary lesions, elevated creatinine, and lower percentage of Tregs significantly influenced PFS.

CONCLUSION

Overall, Tregs at diagnosis were found to be important for predicting early relapse and progression-free survival, highlighting their potential as a biomarker for functional high risk in multiple myeloma.

摘要

目的

本研究调查了调节性T细胞(Tregs)在新诊断的多发性骨髓瘤(NDMM)患者中的作用,特别是与早期复发和预后的关系。

方法

分析纳入了70例NDMM患者的临床资料,在诊断时检测Tregs。早期复发定义为18个月内复发(ER18),移植后生存期超过12个月。基于该标准评估功能高危(FHR)。

结果

对于整个队列,未达到无进展生存期(PFS)和总生存期(OS)的中位数,但在ER18队列中,OS中位数为24.8个月,PFS中位数为10.8个月。与早期复发相关的关键因素包括血清肌酐水平升高(>156μmol/L)、髓外疾病的存在以及诊断时Tregs百分比降低。多因素分析显示,髓外疾病和Tregs百分比降低是早期复发的重要预测因素。年龄、肌酐升高、髓外疾病和Tregs百分比降低等因素与较差的PFS相关。进一步分析证实,髓外病变、肌酐升高和Tregs百分比降低显著影响PFS。

结论

总体而言,发现诊断时的Tregs对于预测早期复发和无进展生存期很重要,突出了它们作为多发性骨髓瘤功能高危生物标志物的潜力。

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本文引用的文献

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Definers and drivers of functional high-risk multiple myeloma: insights from genomic, transcriptomic, and immune profiling.功能性高危多发性骨髓瘤的定义因素和驱动因素:来自基因组、转录组和免疫分析的见解
Front Oncol. 2023 Oct 2;13:1240966. doi: 10.3389/fonc.2023.1240966. eCollection 2023.
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Early relapse within 18 months is a powerful dynamic predictor for prognosis and could revise static risk distribution in multiple myeloma.18 个月内的早期复发是预后的有力动态预测指标,并可修正多发性骨髓瘤的静态风险分布。
Cancer. 2024 Feb 1;130(3):421-432. doi: 10.1002/cncr.35056. Epub 2023 Oct 17.
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Modulating Treg stability to improve cancer immunotherapy.
调节调节性T细胞稳定性以改善癌症免疫疗法。
Trends Cancer. 2023 Nov;9(11):911-927. doi: 10.1016/j.trecan.2023.07.015. Epub 2023 Aug 17.
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Current Main Topics in Multiple Myeloma.多发性骨髓瘤的当前主要议题
Cancers (Basel). 2023 Apr 8;15(8):2203. doi: 10.3390/cancers15082203.
5
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.预测遗传异质性多发性骨髓瘤中免疫治疗结果和免疫逃逸机制的临床前模型。
Nat Med. 2023 Mar;29(3):632-645. doi: 10.1038/s41591-022-02178-3. Epub 2023 Mar 16.
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Multiple myeloma: 2022 update on diagnosis, risk stratification, and management.多发性骨髓瘤:2022 年诊断、风险分层和治疗的更新。
Am J Hematol. 2022 Aug;97(8):1086-1107. doi: 10.1002/ajh.26590. Epub 2022 May 23.
7
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.调节性 T 细胞浸润肿瘤的机制:对创新免疫精准治疗的启示。
J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2021-002591.
8
Emerging immunotherapies in multiple myeloma.多发性骨髓瘤的新兴免疫疗法。
BMJ. 2020 Sep 21;370:m3176. doi: 10.1136/bmj.m3176.
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Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing.基于新一代测序技术的初诊多发性骨髓瘤患者的早期复发风险。
Clin Cancer Res. 2020 Sep 15;26(18):4832-4841. doi: 10.1158/1078-0432.CCR-20-0951. Epub 2020 Jul 2.
10
[The guidelines for the diagnosis and management of multiple myeloma in China(2020 revision)].《中国多发性骨髓瘤诊断与治疗指南(2020年修订版)》
Zhonghua Nei Ke Za Zhi. 2020 May 1;59(5):341-346. doi: 10.3760/cma.j.cn112138-20200304-00179.