Abstract:
Lymphomas represent a group of highly heterogeneous malignant tumors. The tumor microenvironment (TME) surrounding these tumors plays a crucial role in disease progression and the efficacy of therapeutic interventions. Traditional two-dimensional cell culture models fail to accurately recapitulate the inherent complexity of three-dimensional (3D)
in vivo architecture. Organoid technology provides a novel tool for lymphoma research, utilizing 3D culture systems to reconstruct tumor tissue organization and functionality. Despite the potential of this technology,the development of lymphoma organoid models remains a significant challenge. Developing lymphoma organoid models faces numerous hurdles, including replicating the unique biological characteristics of lymphoma and itscomplexmicroenvironment. This study provides a systematic summary of challenges associated with lymphoma organoid construction and describes recent advances in relevant methodologies. Moreover, the study further reviews recent advances in co-culture techniques combining lymphoma organoids and immune cells, including protocols for culturing patient-derived primary central nervous system lymphoma organoids and patient-derived lymphoma organoids. These advances have significantly facilitated the clinical translation of lymphoma research, transitioning it from fundamental mechanistic studies toward personalized and precision therapeutic approaches.