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Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention

Authors

  • T. O'Connor
  • X. Zhou
  • J. Kosla
  • A. Adili
  • M. Garcia Beccaria
  • E. Kotsiliti
  • D. Pfister
  • A.L. Johlke
  • A. Sinha
  • R. Sankowski
  • M. Schick
  • R. Lewis
  • N. Dokalis
  • B. Seubert
  • B. Höchst
  • D. Inverso
  • D. Heide
  • W. Zhang
  • P. Weihrich
  • K. Manske
  • D. Wohlleber
  • M. Anton
  • A. Hoellein
  • G. Seleznik
  • J. Bremer
  • S. Bleul
  • H.G. Augustin
  • F. Scherer
  • U. Koedel
  • A. Weber
  • U. Protzer
  • R. Förster
  • T. Wirth
  • A. Aguzzi
  • F. Meissner
  • M. Prinz
  • B. Baumann
  • U.E. Höpken
  • P.A. Knolle
  • L. von Baumgarten
  • U. Keller
  • M. Heikenwalder

Journal

  • Cancer Cell

Citation

  • Cancer Cell 36 (3): 250-267

Abstract

  • 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.


DOI

doi:10.1016/j.ccell.2019.08.001