Engineering the Immune Microenvironment into Organoid Models

Organoid models have revolutionized cancer research through their ability to capture the cellular heterogeneity and spatial organization of a tumor in 3D culture. Patient-derived organoids can also mirror responses to therapy in vitro, opening the doors to personalized medicine that can direct clinical decision-making. As cancer immunotherapy has flourished and efforts to develop novel immunotherapies have increased, models that incorporate immune cells into organoid coculture to recapitulate the complexity of the tumor microenvironment faithfully are in high demand. To this end, a wide variety of organoid immune coculture methods have been developed, each differing in the source of immune cells used, types of immune cells maintained in culture, and their specific utility. This review aims to organize these methods into a framework that will aid researchers in choosing the appropriate system for their experimental needs. We also highlight several nonimmune cell types that have been successfully incorporated into organoid culture and the biology these coculture models are poised to interrogate. Expected final online publication date for the Annual Review of Cancer Biology, Volume 7 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.