增强适应性免疫是发展下一代癌症治疗的关键目标。渗透到肿瘤中的T和B细胞通过与局部微环境的复杂相互作用极大地影响着癌症进展。癌细胞通过劫持正常的免疫途径来逃避和限制这些免疫反应。目前使用常规原代细胞、细胞株或动物的实验模型对于研究与人类生物学和临床转化直接相关的癌症-免疫相互作用存在局限性。因此，模拟本地和系统水平的这种相互作用的工程方法对于加快开发更好的治疗和诊断工具至关重要。在本综述中，我们讨论了工程肿瘤-免疫微环境（TME）及其适应性免疫的关键元素的挑战、最新进展和未来方向。首先，我们概述了近期研究的进展，这些研究促进了我们对适应性免疫系统在肿瘤微环境中的作用的认识。接下来，我们讨论了最新的三维体外模型和工程方法的发展，这些方法已被用来研究癌细胞和间质细胞与B和T淋巴细胞的相互作用。我们总结了三维生物工程的最新进展，并讨论了需要更好地结合适应性免疫和肿瘤微环境的复杂相互作用元素的三维肿瘤模型。最后，我们提供了针对建模癌症-免疫相互作用的当前挑战和未来方向的展望，旨在为诊断和治疗的新生物学靶点的发现做出贡献。版权所有©2023年Visalakshan、Lowrey、Sousa、Helms、Samiea、Schutt、Moreau和Bertassoni。

Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics.Copyright © 2023 Visalakshan, Lowrey, Sousa, Helms, Samiea, Schutt, Moreau and Bertassoni.