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通过体外微流控球体模型表征 rCHOP 治疗对弥漫性大 B 细胞淋巴瘤微环境的影响

英文原题:Characterizing influence of rCHOP treatment on diffuse large B-cell lymphoma microenvironment through in vitro microfluidic spheroid model.

PubMed 2024/01/09(内容时间) Cell Death Dis Q1 · IF 12.2(JCR 2025)

研究概要

这些发现支持该模型作为新型治疗方法比较筛选的最佳平台。

中文摘要

二十多年来,Rituximab 联合 CHOP 方案(rCHOP)一直是弥漫性大 B 细胞淋巴瘤(DLBCL)的标准治疗方法。尽管大量临床试验探索了替代治疗方案,但很少有方案显示出进一步改善患者生存率和康复率的希望。随着癌症免疫治疗的兴起,近期涌现出一波新的治疗手段,然而临床试验的成本使得所有有前景的方案都难以逐一测试。改进的早期药物筛选方法对于加速开发最有可能帮助患者的治疗手段至关重要。微流控装置提供了强大的药物测试工具,具有增强的生物学相关性以及多参数数据输出。在此,我们描述了一种基于水凝胶球体的微流控模型,用于筛选淋巴瘤治疗方案。我们利用原代患者 DLBCL 细胞,结合 NK 细胞和 rCHOP 治疗,来确定该方法的生物学相关性。我们观察到治疗后的细胞活力、流变学特性以及细胞表面标志物表达水平与预期的体内特征高度吻合。此外,我们探索了治疗后的分泌组和转录组变化。我们的结果显示,对治疗刺激的表型和转录组反应发生了复杂变化,包括众多代谢和免疫原性改变。这些发现支持该模型作为新型治疗手段比较筛选的最佳平台。

展开英文摘要原文

For over two decades, Rituximab and CHOP combination treatment (rCHOP) has remained the standard treatment approach for diffuse large B-cell lymphoma (DLBCL). Despite numerous clinical trials exploring treatment alternatives, few options have shown any promise at further improving patient survival and recovery rates. A wave of new therapeutic approaches have recently been in development with the rise of immunotherapy for cancer, however, the cost of clinical trials is prohibitive of testing all promising approaches. Improved methods of early drug screening are essential for expediting the development of the therapeutic approaches most likely to help patients. Microfluidic devices provide a powerful tool for drug testing with enhanced biological relevance, along with multi-parameter data outputs. Here, we describe a hydrogel spheroid-based microfluidic model for screening lymphoma treatments. We utilized primary patient DLBCL cells in combination with NK cells and rCHOP treatment to determine the biological relevance of this approach. We observed cellular viability in response to treatment, rheological properties, and cell surface marker expression levels correlated well with expected in vivo characteristics. In addition, we explored secretory and transcriptomic changes in response to treatment. Our results showed complex changes in phenotype and transcriptomic response to treatment stimuli, including numerous metabolic and immunogenic changes. These findings support this model as an optimal platform for the comparative screening of novel treatments.

论文信息

作者
Sullivan MR、White RP、Dashnamoorthy Ravi、Kanetkar N、Fridman IB、Ekenseair A、Evens AM、Konry T
第一作者单位
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.United States
通讯作者单位
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA. T.Konry@Northeastern.edu.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Cell death & disease2024 Jan 9
原文标识
PubMed 38195589 · DOI 10.1038/s41419-023-06299-6