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.