Extended human lymph node explants for evaluation of adaptive immunity

Lymph nodes (LNs) are a vital component of the adaptive immune system as they have a key role in antigen presentation and regulation of immune responses. However, preclinical models that accurately mimic the complexity and spatial organization of LNs remain a significant unmet need for the study of LN biology. Here, we leveraged the use of biomaterials to significantly extend the lifespan of patient-derived LN explants ex vivo. Hydrogel-embedded LN explants preserved the cellular composition and maintained the intricate spatial organization of the LN. This enabled the LN explants to retain functional responsiveness, as demonstrated by their ability to mount immune responses after exposure to tumor antigens or SARS-CoV-2 mRNA vaccine. The LN explant models developed in this study offer a robust and physiologically relevant platform for studying immune responses ex vivo, facilitating the development of vaccines and immunotherapies in the context of cancer and infectious diseases.