Gaebler Daniela, Hachey Stephanie J, Hughes Christopher C W
Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States.
Biomedical Engineering, University of California, Irvine, Irvine, CA, United States.
Front Bioeng Biotechnol. 2024 Sep 25;12:1462293. doi: 10.3389/fbioe.2024.1462293. eCollection 2024.
The tumor microenvironment (TME) comprises a diverse array of cells, both cancerous and non-cancerous, including stromal cells and immune cells. Complex interactions among these cells play a central role in driving cancer progression, impacting critical aspects such as tumor initiation, growth, invasion, response to therapy, and the development of drug resistance. While targeting the TME has emerged as a promising therapeutic strategy, there is a critical need for innovative approaches that accurately replicate its complex cellular and non-cellular interactions; the goal being to develop targeted, personalized therapies that can effectively elicit anti-cancer responses in patients. Microfluidic systems present notable advantages over conventional 2D co-culture models and animal models, as they more accurately mimic crucial features of the TME and enable precise, controlled examination of the dynamic interactions among multiple human cell types at any time point. Combining these models with next-generation technologies, such as bioprinting, single cell sequencing and real-time biosensing, is a crucial next step in the advancement of microfluidic models. This review aims to emphasize the importance of this integrated approach to further our understanding of the TME by showcasing current microfluidic model systems that integrate next-generation technologies to dissect cellular intra-tumoral interactions across different tumor types. Carefully unraveling the complexity of the TME by leveraging next generation technologies will be pivotal for developing targeted therapies that can effectively enhance robust anti-tumoral responses in patients and address the limitations of current treatment modalities.
肿瘤微环境（TME）由各种各样的细胞组成，包括癌细胞和非癌细胞，如基质细胞和免疫细胞。这些细胞之间的复杂相互作用在驱动癌症进展中起着核心作用，影响肿瘤起始、生长、侵袭、对治疗的反应以及耐药性发展等关键方面。虽然靶向肿瘤微环境已成为一种有前景的治疗策略，但迫切需要创新方法来准确复制其复杂的细胞和非细胞相互作用；目标是开发能够在患者中有效引发抗癌反应的靶向性、个性化疗法。微流控系统相较于传统的二维共培养模型和动物模型具有显著优势，因为它们能更准确地模拟肿瘤微环境的关键特征，并能在任何时间点对多种人类细胞类型之间的动态相互作用进行精确、可控的检测。将这些模型与生物打印、单细胞测序和实时生物传感等下一代技术相结合，是微流控模型发展的关键下一步。本综述旨在强调这种综合方法的重要性，通过展示当前整合下一代技术以剖析不同肿瘤类型内细胞间相互作用的微流控模型系统，进一步加深我们对肿瘤微环境的理解。利用下一代技术仔细剖析肿瘤微环境的复杂性，对于开发能够有效增强患者强大抗肿瘤反应并解决当前治疗方式局限性的靶向疗法至关重要。
