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

Lisa Kristina Isbell, Cordula Tschuch, Soroush Doostkam, Silvia Waldeck, Geoffroy Andrieux, Khalid Shoumariyeh, Dorothee Lenhard, Hans Eckart Schaefer, Peter Christoph Reinacher, Ingrid Bartsch, Milena Pantic, Janaki Manoja Vinnakota, Vinodh Kakkassery, Elisabeth Schorb, Florian Scherer, Anna Verena Frey, Melanie Boerries, Gerald Illerhaus, Justus Duyster, Julia SchuelerNikolas von Bubnoff*

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Aims: How 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. Methods: We 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. Results: We 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. Conclusion: This 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.

OriginalspracheEnglisch
Aufsatznummere12899
ZeitschriftNeuropathology and Applied Neurobiology
Jahrgang49
Ausgabenummer2
Seiten (von - bis)e12899
ISSN0305-1846
DOIs
PublikationsstatusVeröffentlicht - 04.2023

Strategische Forschungsbereiche und Zentren

  • Profilbereich: Lübeck Integrated Oncology Network (LION)
  • Zentren: Universitäres Cancer Center Schleswig-Holstein (UCCSH)

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