3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade.
3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade.
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DOI：
10.1039/c8lc00322j
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发表时间：
2018-10-09
期刊：
影响因子：
6.1
通讯作者：
Jenkins RW
中科院分区：
文献类型：
--
作者：
Aref AR;Campisi M;Ivanova E;Portell A;Larios D;Piel BP;Mathur N;Zhou C;Coakley RV;Bartels A;Bowden M;Herbert Z;Hill S;Gilhooley S;Carter J;Cañadas I;Thai TC;Kitajima S;Chiono V;Paweletz CP;Barbie DA;Kamm RD;Jenkins RW
微流体培养有可能彻底改变癌症诊断和治疗。事实上，正在开发几种专门用于临床的微型设备，以测试新的癌症治疗方法。为了有效，这些平台需要通过直接的细胞-细胞或细胞-基质接触或通过分泌信号传导因子如细胞因子、趋化因子和生长因子来复制肿瘤微环境的肿瘤细胞和非肿瘤细胞元素之间存在的连续相互作用。鉴于个性化或精确癌症治疗的挑战，特别是随着新型免疫疗法的出现，迫切需要更复杂的离体诊断系统，该系统概括了患者特异性肿瘤生物学，具有实时预测对基于免疫的疗法的反应的潜力。在这里，我们介绍了一种筛选患者肿瘤对免疫检查点阻断疗法的反应的方法的细节，该方法首次在Jenkins et al. Cancer Discovery 2018中报道，并更新了对鼠源性和患者源性器官型肿瘤球体的评价。（MDOTS/PDOTS），包括评估MDOTS中3D微流控培养的要求，证明PDOTS的免疫检查点敏感性，以及使用RNA测序来推断肿瘤免疫微环境的变化的肿瘤免疫相互作用的扩展评估。我们还研究了对当前系统的一些潜在改进，并讨论了将此类诊断检测转化为临床的挑战。
Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy. Indeed, several microdevices are being developed specifically for clinical use to test novel cancer therapeutics. To be effective, these platforms need to replicate the continuous interactions that exist between tumor cells and non-tumor cell elements of the tumor microenvironment through direct cell-cell or cell-matrix contact or by the secretion of signaling factors such as cytokines, chemokines and growth factors. Given the challenges of personalized or precision cancer therapy, especially with the advent of novel immunotherapies, a critical need exists for more sophisticated ex vivo diagnostic systems that recapitulate patient-specific tumor biology with the potential to predicting response to immune-based therapies in real-time. Here, we present details of a method to screen for the response of patient tumors to immune checkpoint blockade therapy, first reported in Jenkins et al. Cancer Discovery 2018, with updated evaluation of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and expanded evaluation of tumor-immune interactions using RNA-sequencing to infer changes in the tumor-immune microenvironment. We also examine some potential improvements to current systems and discuss the challenges in translating such diagnostic assays to the clinic.
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影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
8.8
作者：
Jenkins RW;Barbie DA;Flaherty KT
通讯作者：
Flaherty KT
影响因子：
28.2
作者：
Girotti, Maria Romina;Gremel, Gabriela;Marais, Richard
通讯作者：
Marais, Richard
影响因子：
11.2
作者：
Daniel VC;Marchionni L;Hierman JS;Rhodes JT;Devereux WL;Rudin CM;Yung R;Parmigiani G;Dorsch M;Peacock CD;Watkins DN
通讯作者：
Watkins DN
影响因子：
5.6
作者：
Arrigoni C;Bersini S;Gilardi M;Moretti M
通讯作者：
Moretti M