A hallmark of primary lymphoma of the central nervous system (CNS; PCNSL) is the strong
CXCR4 expression of the tumor cells, the function of which is still unknown. In vitro treatment of BAL17CNS lymphoma cells by AMD3100, which inhibits CXCR4-CXCL12 interactions, resulted in
the significantly differential expression of 273 genes encoding proteins involved
in cell motility, cell-cell signaling and interaction, hematological system development
and function, and immunologic disease. Among the genes down-regulated was the one
encoding CD200, a regulator of CNS immunologic activity. These data directly translated
into the in vivo situation; BAL17CNS CD200 expression was down-regulated by 89% (3% versus 28% CD200+ lymphoma cells) in AMD3100-treated versus untreated mice with BAL17CNS-induced PCNSL. Reduced lymphoma cell CD200 expression may contribute to the markedly
increased microglial activation in AMD3100-treated mice. AMD3100 also maintained the
structural integrity of blood-brain barrier tight junctions and the outer basal lamina
of cerebral blood vessels. Subsequently, lymphoma cell invasion of the brain parenchyma
was impaired, and maximal parenchymal tumor size was significantly reduced by 82%
in the induction phase. Thus, AMD3100 qualified as a potentially attractive candidate
to be included into the therapeutic concept of PCNSL. Beyond therapy, CXCR4-induced
suppression of microglial activity is of general neuroimmunologic interest and identifies
CD200 expressed by the lymphoma cells as a novel mechanism of immune escape in PCNSL.
Graphical abstract
Graphical Abstract
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Article info
Publication history
Published online: May 15, 2023
Accepted:
April 26,
2023
Publication stage
In Press Journal Pre-ProofFootnotes
Supported by Deutsche Krebshilfe 70112052 and 70112053 (M.D. and R.S.); and Wilhelm-Sander Stiftung 2011.092.2 and 2020.149.1 (M.D. and M.M.-R.).
Disclosures: None declared.
Current address of A.B., Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; of M.D., Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Identification
Copyright
© 2023 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.
