Cancer Cell
Volume 36, Issue 3, 16 September 2019, Pages 250-267.e9
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Article
Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention

https://doi.org/10.1016/j.ccell.2019.08.001Get rights and content
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Highlights

  • Gliosis increases the risk for central nervous system lymphoma

  • Lymphoma cell enter the healthy brain parenchyma but exit quickly due to endothelial CXCL12

  • Astrocytic CCL19 counteracts CXCL12 and retains lymphoma cells in the parenchyma

  • Aged brains express more CCL19 and are more susceptible to forming CNS lymphomas

Summary

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.

Keywords

CNSL
PCNSL
SCNSL
gliosis
CCL19
metastasis
lymphoma
DLBCL
neuroinflammation
CXCL12

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