Bioengineering translational models of lymphoid tissues

Bioengineered models of human tissues have the potential to revolutionize human health by providing a translational platform to investigate disease mechanisms and develop new therapies. Recreating human immune biology is challenging owing to its unique complexity and diversity at the molecular, cellular, tissue and system levels. Advances in immunotherapy have contributed to the emergence of immuno-engineering as a new discipline that applies engineering principles to modulate and emulate the immune system. In synergy with single-cell sequencing, spatial omics, systems immunology, organoids and organ-on-a-chip technologies, these are helping to decipher and recreate human immune components and responses in vitro at a high level of biological fidelity. In this Review, we contextualize the needs for predictive non-clinical models of human immune responses and we overview recent advances in bioengineering models of lymphoid tissues and immune-competent non-lymphoid tissues. We focus on models of the thymus, lymph nodes and intestinal mucosa as examples requiring different degrees of biological and technical complexity. We highlight the experimental demonstrations of their translational value and propose avenues to boost their impact as non-clinical models for immunotherapies.