Creating artificial lymphoid tissues to study immunity and hematological malignancies.

Abstract

The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions. Thus, artificial tissues are being developed to study these interactions in the context of immune development, function, and disease. New bone marrow and lymph node models have been created to, respectively, study microenvironmental interactions in hematopoiesis and germinal center-like biology. These models have also been extended to understand the effect of these interactions on the progression and therapeutic response in leukemia, multiple myeloma, and lymphoma. 3D in-vitro immune models have elucidated new cellular, biochemical, and biophysical interactions as potential regulatory mechanisms, therapeutic targets, or biomarkers that previously could not be studied in animal models and conventional 2D cultures. Incorporation of advanced biomaterials, microfluidics, genome editing, and single-cell analysis tools will enable further studies of function, driver mutations, and tumor heterogeneity. Continual refinement will help inform the development of antibody and cell-based immunotherapeutics and patient-specific treatment plans.