Moll Maximilian, Baumjohann Dirk
Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
EMBO Mol Med. 2025 Mar;17(3):385-394. doi: 10.1038/s44321-025-00193-8. Epub 2025 Jan 27.
Studying the human immune system in vivo is challenging and often not possible. Therefore, most human immunology studies have been predominantly confined to peripheral blood analyses, which by themselves have inherent limitations, as many immune reactions take place within tissues. For example, potent antibody responses that contribute to fighting infections and provide protection following vaccination require cellular interactions between B cells and T cells in specialized micro-anatomical structures called germinal centers, which are found in secondary lymphoid organs such as spleen, lymph nodes, and tonsils. Thus, there is a clear demand for novel enhanced experimental systems that faithfully recapitulate the intricate dynamics of the human immune system as much as possible. In this review, we discuss recent advances in versatile human tonsil/adenoid tissue-based ex vivo immune organoid cultures as well as related cancer and autoimmunity-focused experimental setups. These systems have been implemented as translational immunology platforms for in-depth analyses of human B and T cell-mediated immune responses, thereby facilitating mechanistic studies as well as drug and vaccine testing in a human-first approach.
在体内研究人类免疫系统具有挑战性，而且往往无法实现。因此，大多数人类免疫学研究主要局限于外周血分析，而外周血分析本身存在固有局限性，因为许多免疫反应发生在组织内。例如，有效的抗体反应有助于抵抗感染并在接种疫苗后提供保护，这需要B细胞和T细胞在称为生发中心的特殊微解剖结构中进行细胞间相互作用，生发中心存在于脾脏、淋巴结和扁桃体等二级淋巴器官中。因此，迫切需要新型增强实验系统，尽可能忠实地重现人类免疫系统的复杂动态。在这篇综述中，我们讨论了基于人类扁桃体/腺样体组织的多功能体外免疫类器官培养以及相关的以癌症和自身免疫为重点的实验设置的最新进展。这些系统已被用作转化免疫学平台，用于深入分析人类B细胞和T细胞介导的免疫反应，从而以人类优先的方法促进机制研究以及药物和疫苗测试。
