3D Culture Systems for Exploring Cancer Immunology

Simple Summary To study any disease, researchers need convenient and relevant disease models. In cancer, the most commonly used models are two-dimensional (2D) culture models, which grow cells on hard, rigid, plastic surfaces, and mouse models. Cancer immunology is especially difficult to model because the immune system is exceedingly complex; it contains multiple types of cells, and each cell type has several subtypes and a spectrum of activation states. These many immune cell types interact with cancer cells and other components of the tumor, ultimately influencing disease outcomes. 2D culture methods fail to recapitulate these complex cellular interactions. Mouse models also suffer because the murine and human immune systems vary significantly. Three-dimensional (3D) culture systems therefore provide an alternative method to study cancer immunology and can fill the current gaps in available models. This review will describe common 3D culture models and how those models have been used to advance our understanding of cancer immunology. Cancer immunotherapy has revolutionized cancer treatment, spurring extensive investigation into cancer immunology and how to exploit this biology for therapeutic benefit. Current methods to investigate cancer-immune cell interactions and develop novel drug therapies rely on either two-dimensional (2D) culture systems or murine models. However, three-dimensional (3D) culture systems provide a potentially superior alternative model to both 2D and murine approaches. As opposed to 2D models, 3D models are more physiologically relevant and better replicate tumor complexities. Compared to murine models, 3D models are cheaper, faster, and can study the human immune system. In this review, we discuss the most common 3D culture systems-spheroids, organoids, and microfluidic chips-and detail how these systems have advanced our understanding of cancer immunology.