Characterizing influence of rCHOP treatment on diffuse large B-cell lymphoma microenvironment through in vitro microfluidic spheroid model.
Characterizing influence of rCHOP treatment on diffuse large B-cell lymphoma microenvironment through in vitro microfluidic spheroid model.
复制标题
DOI：
10.1038/s41419-023-06299-6
复制
发表时间：
2024-01-09
影响因子：
9
通讯作者：
Konry, Tania
中科院分区：
文献类型：
--
作者：
Sullivan, Matthew R.;White, Rachel P.;Ravi, Dashnamoorthy;Kanetkar, Ninad;Fridman, Ilana Berger;Ekenseair, Adam;Evens, Andrew M.;Konry, Tania
20多年来，利妥昔单抗和CHOP联合治疗（rCHOP）一直是弥漫性大b细胞淋巴瘤（DLBCL）的标准治疗方法。尽管有许多临床试验探索治疗方案，但很少有方案显示出进一步提高患者生存率和治愈率的希望。随着癌症免疫疗法的兴起，最近出现了一波新的治疗方法，然而，临床试验的成本令人望而却步，无法测试所有有希望的方法。改进早期药物筛选方法对于加快最有可能帮助患者的治疗方法的发展至关重要。微流控装置为药物测试提供了强大的工具，具有增强的生物学相关性，以及多参数数据输出。在这里，我们描述了一个基于水凝胶球的微流控模型，用于筛选淋巴瘤治疗。我们利用原发性患者DLBCL细胞联合NK细胞和rCHOP治疗来确定这种方法的生物学相关性。我们观察到细胞活力对治疗的反应、流变特性和细胞表面标记物表达水平与预期的体内特征密切相关。此外，我们还探讨了治疗后的分泌和转录组变化。我们的研究结果显示，对治疗刺激的表型和转录组反应发生了复杂的变化，包括许多代谢和免疫原性变化。这些发现支持该模型作为比较筛选新疗法的最佳平台。
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.
登录
查看更多内容
影响因子：
4.7
作者：
通讯作者：
--
影响因子：
11.2
作者：
Ho, Weng Tong;Pang, Wan Lu;Schwarz, Herbert
通讯作者：
Schwarz, Herbert
DOI：
10.1084/jem.20200839
发表时间：
2021-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Deuse T;Hu X;Agbor-Enoh S;Jang MK;Alawi M;Saygi C;Gravina A;Tediashvili G;Nguyen VQ;Liu Y;Valantine H;Lanier LL;Schrepfer S
通讯作者：
Schrepfer S
DOI：
10.1093/annonc/mdy450
发表时间：
2018-12-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Ciavarella S;Vegliante MC;Fabbri M;De Summa S;Melle F;Motta G;De Iuliis V;Opinto G;Enjuanes A;Rega S;Gulino A;Agostinelli C;Scattone A;Tommasi S;Mangia A;Mele F;Simone G;Zito AF;Ingravallo G;Vitolo U;Chiappella A;Tarella C;Gianni AM;Rambaldi A;Zinzani PL;Casadei B;Derenzini E;Loseto G;Pileri A;Tabanelli V;Fiori S;Rivas-Delgado A;López-Guillermo A;Venesio T;Sapino A;Campo E;Tripodo C;Guarini A;Pileri SA
通讯作者：
Pileri SA
影响因子：
3.4
作者：
Bikmulina, Polina;Kosheleva, Nastasia;Shpichka, Anastasia
通讯作者：
Shpichka, Anastasia