Patient-derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma

AimsHow and why lymphoma cells home to the central nervous system and vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system remain unknown. Our aim was to create an in vivo model to study lymphoma cell tropism to the central nervous system. MethodsWe established a patient-derived central nervous system lymphoma xenograft mouse model and characterised xenografts derived from four primary and four secondary central nervous system lymphoma patients using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In reimplantation experiments, we analysed dissemination patterns of orthotopic and heterotopic xenografts and performed RNA sequencing of different involved organs to detect differences at the transcriptome level. ResultsWe found that xenografted primary central nervous system lymphoma cells home to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed distinct signatures for lymphoma cells in the brain in comparison to the spleen as well as a small overlap of commonly regulated genes in both primary and secondary central nervous system lymphoma. ConclusionThis in vivo tumour model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways for the central nervous system and retinal tropism with the goal to find new targets for novel therapeutic approaches.

Automated summary

This study established a patient-derived central nervous system lymphoma xenograft mouse model, which successfully mimicked the pathology of central nervous system lymphoma and primary vitreoretinal lymphoma. Transcriptomic analysis revealed distinct gene regulation patterns between these two types of lymphoma. This model provides a valuable tool for studying the mechanisms of lymphoma cell tropism to the central nervous system and identifying potential therapeutic targets.