Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology.
Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology.
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随波逐流：用微流控技术模拟肿瘤微环境。
DOI：
10.3390/cancers13236052
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发表时间：
2021-12-01
期刊：
影响因子：
5.2
通讯作者：
Jenkins RW
中科院分区：
文献类型：
--
作者：
Xie H;Appelt JW;Jenkins RW
针对免疫检查点(如PD-1、CTLA-4)的肿瘤免疫治疗的临床成功开启了癌症治疗的新纪元，旨在促进抗肿瘤免疫，希望为晚期转移性癌症患者提供持久的临床反应。这一成功也重新激发了人们对开发肿瘤模型系统的兴趣，这些系统概括了抗肿瘤免疫反应的关键特征，以补充现有的体内肿瘤模型。近年来出现了病人来源的肿瘤模型，以促进肿瘤免疫动力学的研究。微流控技术使评价肿瘤微环境的微生理系统(MPSS)的发展成为可能，这些系统在研究肿瘤免疫动力学方面显示出早期的前景。进一步发展基于微流控的“芯片上肿瘤”MPSS来研究肿瘤与免疫的相互作用，可能会克服目前肿瘤免疫学面临的几个关键挑战。癌症免疫治疗的最新进展导致了多种恶性肿瘤治疗模式的转变，重新关注宿主免疫系统和肿瘤免疫动力学。然而，免疫治疗的内在和获得性耐药性限制了患者的利益和更广泛的应用。对免疫治疗的反应和抵抗机制的研究已经揭示了关键的肿瘤内在因素和肿瘤外在因素。研究与多种细胞类型的复杂相互作用对于了解癌症治疗的反应和耐药机制是必要的。缺乏能够真实概括肿瘤微环境(TME)关键特征的模型系统仍然是癌症研究人员面临的一个挑战。在这里，我们综述了TME模型的最新进展，重点是使用微流控技术来研究和模拟TME，包括应用微流控技术来研究肿瘤免疫动力学和对癌症治疗的反应。我们还讨论了当前系统的局限性，并提出了未来利用这项技术的最大潜力的方向。
The clinical success of cancer immunotherapy targeting immune checkpoints (e.g., PD-1, CTLA-4) has ushered in a new era of cancer therapeutics aimed at promoting antitumor immunity in hopes of offering durable clinical responses for patients with advanced, metastatic cancer. This success has also reinvigorated interest in developing tumor model systems that recapitulate key features of antitumor immune responses to complement existing in vivo tumor models. Patient-derived tumor models have emerged in recent years to facilitate study of tumor–immune dynamics. Microfluidic technology has enabled development of microphysiologic systems (MPSs) for the evaluation of the tumor microenvironment, which have shown early promise in studying tumor–immune dynamics. Further development of microfluidic-based “tumor-on-a-chip” MPSs to study tumor–immune interactions may overcome several key challenges currently facing tumor immunology. Recent advances in cancer immunotherapy have led a paradigm shift in the treatment of multiple malignancies with renewed focus on the host immune system and tumor–immune dynamics. However, intrinsic and acquired resistance to immunotherapy limits patient benefits and wider application. Investigations into the mechanisms of response and resistance to immunotherapy have demonstrated key tumor-intrinsic and tumor-extrinsic factors. Studying complex interactions with multiple cell types is necessary to understand the mechanisms of response and resistance to cancer therapies. The lack of model systems that faithfully recapitulate key features of the tumor microenvironment (TME) remains a challenge for cancer researchers. Here, we review recent advances in TME models focusing on the use of microfluidic technology to study and model the TME, including the application of microfluidic technologies to study tumor–immune dynamics and response to cancer therapeutics. We also discuss the limitations of current systems and suggest future directions to utilize this technology to its highest potential.
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影响因子：
4.6
作者：
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通讯作者：
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82.9
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Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
6.1
作者：
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通讯作者：
Jenkins RW