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文章:

新诊断肉瘤儿童、青少年及年轻成人细胞因子谱分析揭示IL-1β在骨肉瘤转移中的作用

Cytokine Profiling of Children, Adolescents, and Young Adults Newly Diagnosed with Sarcomas Demonstrates the Role of IL-1β in Osteosarcoma Metastasis

原文发布日期:15 September 2025

DOI: 10.3390/cancers17183009

类型: Article

开放获取: 是

 

英文摘要:

Background:Sarcomas are a heterogeneous group of mesenchymal tumors frequently diagnosed in pediatric and young adult patients. These tumors respond poorly to conventional immunotherapy, although the precise reason for this is not known. We sought to characterize the systemic immune response to sarcomas by measuring the levels of circulating cytokines in the plasma of newly diagnosed sarcoma patients, testing the hypothesis that the nature of a patient’s immune response to their tumor directly affects outcome.Methods:Plasma was collected from newly diagnosed, treatment-naive pediatric sarcoma patients participating in an ongoing clinical trial, MCC20320. A panel of 18 cytokines was selected, and cytokine levels were measured using the Luminex platform. Cytokine levels were analyzed based on clinicopathological parameters such as gender, age, stage, and survival.Results:We found that the cytokine profile in patients newly diagnosed with sarcoma is distinct from healthy controls, but different sarcomas were not distinguishable. Patients with osteosarcoma who had elevated levels of multiple cytokines had inferior overall survival compared to those with fewer or no elevated levels. Similarly, elevated levels of individual cytokines and chemokines, including IL-24, CXCL5, and CXCL10, were associated with inferior event-free or overall survival in patients with osteosarcoma. Perhaps most significantly, elevated IL-1β at diagnosis was associated with metastatic presentation and inferior event-free survival in patients with osteosarcoma.Conclusions:These findings suggest that pediatric sarcoma patients mount a systemic immune response that may affect event-free or overall survival. IL-1β in particular may be a valuable therapeutic target for osteosarcoma patients.

 

摘要翻译: 

背景:肉瘤是一组异质性间叶组织肿瘤,常见于儿童及青少年患者。尽管具体原因尚不明确,但这类肿瘤对传统免疫疗法反应不佳。本研究通过检测新诊断肉瘤患者血浆中的循环细胞因子水平,旨在系统性表征机体对肉瘤的免疫应答特征,验证患者对肿瘤的免疫反应性质直接影响预后的假说。 方法:从参与MCC20320临床试验的新诊断、未接受过治疗的儿童肉瘤患者中采集血浆样本。选取18种细胞因子组成检测组合,采用Luminex平台测定细胞因子水平。根据性别、年龄、分期及生存状况等临床病理参数对细胞因子水平进行分析。 结果:研究发现新诊断肉瘤患者的细胞因子谱与健康对照组存在显著差异,但不同肉瘤亚型间无特异性区分。在骨肉瘤患者中,多种细胞因子水平升高者的总生存期较升高因子较少或无升高者更差。同样,包括IL-24、CXCL5和CXCL10在内的特定细胞因子及趋化因子水平升高,与骨肉瘤患者无事件生存期或总生存期缩短相关。最具临床意义的是,诊断时IL-1β水平升高与骨肉瘤患者转移性表现及较差的无事件生存期显著相关。 结论:这些发现表明儿童肉瘤患者会引发系统性免疫反应,该反应可能影响无事件生存期或总生存期。IL-1β尤其可能成为骨肉瘤患者有价值的治疗靶点。

 

 

原文链接:

Cytokine Profiling of Children, Adolescents, and Young Adults Newly Diagnosed with Sarcomas Demonstrates the Role of IL-1β in Osteosarcoma Metastasis

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