Zhang Jie, Tavakoli Hamed, Ma Lei, Li Xiaochun, Han Lichun, Li XiuJun
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China; Department of Chemistry and Biochemistry, University of Texas at El Paso, 500 W University Ave., El Paso, TX 79968, USA.
Department of Chemistry and Biochemistry, University of Texas at El Paso, 500 W University Ave., El Paso, TX 79968, USA.
Adv Drug Deliv Rev. 2022 Aug;187:114365. doi: 10.1016/j.addr.2022.114365. Epub 2022 Jun 3.
Cancer immunotherapy has achieved remarkable success over the past decade by modulating patients' own immune systems and unleashing pre-existing immunity. However, only a minority of cancer patients across different cancer types are able to benefit from immunotherapy treatment; moreover, among those small portions of patients with response, intrinsic and acquired resistance remains a persistent challenge. Because the tumor microenvironment (TME) is well recognized to play a critical role in tumor initiation, progression, metastasis, and the suppression of the immune system and responses to immunotherapy, understanding the interactions between the TME and the immune system is a pivotal step in developing novel and efficient cancer immunotherapies. With unique features such as low reagent consumption, dynamic and precise fluid control, versatile structures and function designs, and 3D cell co-culture, microfluidic tumor organoid-on-a-chip platforms that recapitulate key factors of the TME and the immune contexture have emerged as innovative reliable tools to investigate how tumors regulate their TME to counteract antitumor immunity and the mechanism of tumor resistance to immunotherapy. In this comprehensive review, we focus on recent advances in tumor organoid-on-a-chip platforms for studying the interaction between the TME and the immune system. We first review different factors of the TME that recent microfluidic in vitro systems reproduce to generate advanced tools to imitate the crosstalk between the TME and the immune system. Then, we discuss their applications in the assessment of different immunotherapies' efficacy using tumor organoid-on-a-chip platforms. Finally, we present an overview and the outlook of engineered microfluidic platforms in investigating the interactions between cancer and immune systems, and the adoption of patient-on-a-chip models in clinical applications toward personalized immunotherapy.
在过去十年中，癌症免疫疗法通过调节患者自身的免疫系统并释放预先存在的免疫力取得了显著成功。然而，在不同癌症类型的患者中，只有少数人能够从免疫疗法中获益；此外，在那些有反应的小部分患者中，内在和获得性耐药仍然是一个持续的挑战。由于肿瘤微环境（TME）在肿瘤的发生、发展、转移以及免疫系统的抑制和对免疫疗法的反应中起着关键作用，了解TME与免疫系统之间的相互作用是开发新型高效癌症免疫疗法的关键一步。具有低试剂消耗、动态精确的流体控制、多功能结构和功能设计以及3D细胞共培养等独特特征的微流控肿瘤类器官芯片平台，能够重现TME和免疫环境的关键因素，已成为研究肿瘤如何调节其TME以对抗抗肿瘤免疫以及肿瘤对免疫疗法耐药机制的创新可靠工具。在这篇综述中，我们重点关注用于研究TME与免疫系统相互作用的肿瘤类器官芯片平台的最新进展。我们首先回顾了最近的微流控体外系统重现的TME的不同因素，以生成模仿TME与免疫系统之间相互作用的先进工具。然后，我们讨论了它们在使用肿瘤类器官芯片平台评估不同免疫疗法疗效方面的应用。最后，我们概述并展望了工程化微流控平台在研究癌症与免疫系统相互作用方面的应用，以及患者芯片模型在个性化免疫疗法临床应用中的采用情况。
