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难治性软组织肉瘤患者曲贝替定治疗的免疫监测——IMMUNYON 研究

英文原题:Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study.

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Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study.

PubMed 2025/02/11(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

这些发现支持在未来的临床试验中进一步研究免疫监测。

中文摘要

软组织肉瘤(STS)涵盖超过50种组织学亚型,占实体肿瘤的1%以上。标准治疗包括手术切除及针对晚期病例的蒽环类药物或曲贝替定等疗法,然而由于肿瘤微环境的复杂性和有限的免疫谱分析数据,挑战依然存在。本研究评估了22例难治性STS患者接受曲贝替定治疗的效果,分析了无进展生存期(PFS)和免疫反应。免疫监测包括深度免疫表型分析(200余项参数)、基因表达谱分析(103个基因)和可溶性蛋白质组分析(99种分析物)。根据RECIST1.1标准,68.2%的患者达到疾病稳定(SD),而31.8%的患者表现为疾病进展(PD)。治疗持续时间显示,59.1%的患者治疗不足12个月(<12M),40.9%的患者治疗达12个月或以上(≥12M)。在SD与PD患者中观察到显著的PFS改善(p=0.0154),而治疗持续时间无显著影响(p=0.5433)。PD患者显示嗜酸性粒细胞(p<0.05)和Th2细胞(p<0.05)减少。基因表达分析识别出PD与SD患者中BTRC(降低)、IFNA1(升高)和IL9(升高)的变化(p<0.05)。治疗≥12M的患者表现出活化的HLA-DR Th2细胞增加(p<0.05)以及耗竭B细胞和NK细胞亚群减少(p<0.05)。主成分分析和层次聚类分析识别出与RECIST1.1和治疗持续时间相关的独特免疫谱,强调了免疫谱分析在理解治疗反应中的作用。这些发现支持在未来的临床试验中进一步研究免疫监测。

展开英文摘要原文

Soft tissue sarcomas (STS) encompass over 50 histologic subtypes, representing more than 1% of solid tumors. Standard treatments include surgical resection and therapies such as anthracyclines or trabectedin for advanced cases, though challenges persist due to the tumor microenvironment's complexity and limited immune profiling data. This study evaluates Trabectedin therapy in 22 refractory STS patients, analyzing progression-free survival (PFS) and immune responses. Immune monitoring included deep immunophenotyping (200+ parameters), gene expression profiling (103 genes), and soluble proteome analysis (99 analytes). Using RECIST1.1 criteria, 68.2% of patients achieved stable disease (SD), while 31.8% exhibited progression disease (PD). Therapy duration revealed 59.1% treated for less than 12 months (<12M) and 40.9% for 12 or more months ( 12M). A significant PFS improvement was observed in SD versus PD patients (p=0.0154), while therapy duration showed no effect (p=0.5433). PD patients showed reduced eosinophils (p<0.05) and Th2 cells (p<0.05). Gene expression analysis identified changes in BTRC (decreased), IFNA1 (increased), and IL9 (increased) in PD versus SD patients (p<0.05). Patients treated 12M exhibited increased activated HLA-DR Th2 cells (p<0.05) and decreased exhausted B cells and NK cell subsets (p<0.05). Principal component and hierarchical clustering analyses identified distinct immune profiles associated with RECIST1.1 and therapy duration, underscoring immune profiling's role in understanding treatment responses. These findings support further research into immune monitoring for future clinical trials.

论文信息

作者
Rodrigues-Santos P、Almeida JS、Sousa LM、Couceiro P、Martinho A、Rodrigues J、Fonseca R、Santos-Rosa M
第一作者单位
Laboratory of Immunology and Oncology, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.Portugal
通讯作者单位
Center for Investigation in Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, Portugal.Portugal
期刊
Frontiers in immunology2025
原文标识
PubMed 40007535 · DOI 10.3389/fimmu.2025.1516793