Abstract
Organoids are three-dimensional structures that closely resemble the architecture and functions of human organs, offering key advantages over traditional models by better replicating tissue complexity and cellular interactions. These systems have become invaluable tools for disease modeling, drug screening, and regenerative medicine applications. Despite this progress, their lack of immune components limits their usefulness in diseases where immune cells are central drivers of pathology and therapy. The absence of an immune system within organoids limits their physiological relevance, particularly for cancer, inflammation, and autoimmunity research. Immune cell-containing organoids provide a comprehensive platform for immunotherapy, host-pathogen interactions, regeneration, and immune disorders. This review first highlights the transformative potential of immune cell-containing organoids across cancer, infection, inflammation, autoimmunity, regeneration, and the modeling of primary lymphoid organs. It then examines current strategies for integrating immune cells into organoids, the variety of immune cell sources employed, and the challenges in maintaining immune cell function. Finally, the role of bioengineering, biobanking, and artificial intelligence in overcoming existing limitations and enhancing immune system modeling is discussed. Overall, this study positions immune cell-containing organoids as powerful platforms for translational research and precision medicine.