Cancer thrives in a complex environment where interactions between cellular and acellular components, surrounding the tumor, play a crucial role in disease development and progression. Despite significant progress in cancer research, the mechanism driving tumor growth and therapeutic outcomes remains elusive. Two-dimensional (2D) cell culture assays and in vivo animal models are commonly used in cancer research and therapeutic testing. However, these models suffer from numerous shortcomings including lack of key features of the tumor microenvironment (TME) & cellular composition, cost, and ethical clearance. To that end, there is an increased interest in incorporating and elucidating the influence of TME on cancer progression. Advancements in 3D-engineered ex vivo models, leveraging biomaterials and microengineering technologies, have provided an unprecedented ability to reconstruct native-like bioengineered cancer models to study the heterotypic interactions of TME with a spatiotemporal organization. These bioengineered cancer models have shown excellent capabilities to bridge the gap between oversimplified 2D systems and animal models. In this review article, we primarily provide an overview of the immune and stromal cellular components of the TME and then discuss the latest state-of-the-art 3D-engineered ex vivo platforms aiming to recapitulate the complex TME features. The engineered TME model, discussed herein, are categorized into three main sections according to the cellular interactions within TME: (i) Tumor-Stromal interactions, (ii) Tumor-Immune interactions, and (iii) Complex TME interactions. Finally, we will conclude the article with a perspective on how these models can be instrumental for cancer translational studies and therapeutic testing.

中文翻译：

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设计 3D 离体模型，以概括肿瘤微环境中复杂的基质和免疫相互作用


癌症在复杂的环境中茁壮成长，其中肿瘤周围的细胞和非细胞成分之间的相互作用在疾病发展和进展中起着至关重要的作用。尽管癌症研究取得了重大进展，但驱动肿瘤生长和治疗结果的机制仍然难以捉摸。二维 （2D） 细胞培养测定和体内动物模型通常用于癌症研究和治疗检测。然而，这些模型存在许多缺点，包括缺乏肿瘤微环境（TME）的关键特性和细胞组成、成本和道德审批。为此，人们对纳入和阐明 TME 对癌症进展的影响越来越感兴趣。利用生物材料和微工程技术的 3D 工程离体模型的进步为重建天然生物工程癌症模型提供了前所未有的能力，以研究 TME 与时空组织的异型相互作用。这些生物工程癌症模型已显示出卓越的能力，可以弥合过度简化的 2D 系统和动物模型之间的差距。在这篇综述文章中，我们主要概述了 TME 的免疫和基质细胞成分，然后讨论了最新的最先进的 3D 工程离体平台，旨在概括复杂的 TME 特征。根据 TME 内的细胞相互作用，本文讨论的工程化 TME 模型分为三个主要部分：（i） 肿瘤-基质相互作用，（ii） 肿瘤-免疫相互作用，以及 （iii） 复杂的 TME 相互作用。最后，我们将从这些模型如何有助于癌症转化研究和治疗测试的角度来结束本文。