The role of chronic neuroinflammation in the pathogenesis of CNS lymphoma

• Applicant: Professor Dr. Mathias Heikenwälder
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 361358042

Central nervous system lymphoma (CNSL) is a fatal malignancy with limited treatment options. The mechanisms by which lymphoma cells enter and proliferate in the normally immune-privileged CNS in immunocompetent individuals are currently unknown. We have developed mouse models of CNSL based on constitutive activation of either alternative or canonical NFkB signaling in astrocytes, which strongly promotes the invasion of diverse B-lymphoma cells into mouse brains. These murine B-lymphoma infiltrates express numerous markers found in human CNSL and respond to standard treatments for CNSL in the expected manner. We have used these mice to identify a number of pro-inflammatory mechanisms which might promote the growth of malignant B-cells in nervous tissue, including upregulation of adhesion molecules and production of cytokines that promote B-cell growth. The aim of the current study is to further explore the mechanisms by which neuroinflammation promotes the development of CNS lymphoma and determine whether evidence for similar mechanisms exist in human CNS lymphoma biopsies and patients with non-specific gliosis.

• DFG Programme: Research Grants